leptin and Proteinuria

This study was conducted to examine the effects of weight reduction on proteinuria, adipokines, and renal function in overweight immunoglobulin A nephropathy (IgAN) patients (body mass index > 23 kg/m2) with chronic proteinuria more than 6 months.. This was a single-center, prospective, randomized controlled trial. The study was performed at the outpatient clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from July 2012 to February 2013.. Twenty-six overweight patients with chronic proteinuric biopsy-proven IgAN were randomized into a control group (n = 13) or a low-calorie normal protein diet group (n = 13). All patients received the maximum dosage of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and other antihypertensive agents to achieve a blood pressure less than 125/75 mmHg.. The study intervention was a low-calorie diet (target energy per day as 500-kcal subtraction from total energy requirement) for a 6-month period.. At baseline and after 6 months of a low-calorie diet, body weight, body content, and clinical and laboratory parameters were determined and compared.. After initiating a low-calorie diet for 6 months, the normalized protein nitrogen appearance values were not different, indicating comparable protein intake. The low-calorie group had lower total daily calorie intake (1,307.1 ± 171.8 vs. 1,772.2 ± 315.4 kcal/d, P < .01) and significant reductions in body weight (-5.1 ± 3.3%, P < .001), fat content (-12.7 ± 14.1%, P < .05), and 24-hour urine protein (-45.2 ± 15.4%, P < .001). Blood pressure and renal function parameters were unaltered. The low-calorie group had approximately 20% lower plasma levels of leptin but unchanged adiponectin. There were positive correlations between the amount of protein reduction and the changes of body weight, fat mass, and leptin.. A 6-month low-calorie diet leads to weight reduction and results in diminished fat content and decreased proteinuria in overweight IgAN patients with chronic proteinuria. This beneficial effect might be mediated by changes in adipokines.

Topics: Adiponectin; Adult; Blood Pressure; Body Composition; Caloric Restriction; Dietary Proteins; Female; Glomerulonephritis, IGA; Humans; Leptin; Male; Middle Aged; Overweight; Prospective Studies; Proteinuria; Thailand; Weight Loss

Some angiotensin receptor blockers (ARBs), including irbesartan, increase the peroxisome proliferator-activated receptor (PPAR)-g activity in vitro. The aim of this study was to evaluate the interactions between obesity and the effects of irbesartan on inflammatory cytokines in chronic glomerulonephritis patients without diabetes.. The anti-inflammatory effects of irbesartan were evaluated in 29 hypertensive chronic glomerulonephritis patients without diabetes in a prospective, single-arm study.. Following treatment with irbesartan for 26 weeks, blood pressure and proteinuria significantly decreased, as previously reported (blood pressure decreased from 142±1/87±1 to 131±1/81±1 mmHg and the urine protein/creatinine ratio decreased from 1030±143 to 779±121 mg/g Cr). BMI did not significantly change after the study. Among the inflammatory parameters, the concentrations of adiponectin and high-sensitivity C-reactive protein (hsCRP) significantly improved after treatment; however, the changes in the concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-a and leptin did not reach statistical significance. Moreover, the changes in these five parameters following treatment were moderately correlated with the BMI values obtained at the initiation of the study, and the improvements were particularly prominent in those with a BMI greater than 25. Improvements in proteinuria were significantly correlated with increases in the adiponectin concentration, but not with BMI. There was also a moderate correlation between the changes in the adiponectin and insulin concentrations.. Irbesartan improves metabolic parameters in nondiabetic hypertensive chronic glomerulonephritis patients, especially those with a high BMI. Improving the adiponectin concentration may be important for reducing proteinuria.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Body Mass Index; C-Reactive Protein; Chronic Disease; Cytokines; Female; Glomerulonephritis; Humans; Hypertension; Inflammation Mediators; Interleukin-6; Irbesartan; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Proteinuria; Tetrazoles; Tumor Necrosis Factor-alpha

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.

Topics: Animals; Blood Pressure; Bufanolides; Endothelin-1; Endothelium, Vascular; Female; Intercellular Adhesion Molecule-1; Leptin; Pre-Eclampsia; Pregnancy; Proteinuria; Rats; Rats, Sprague-Dawley; Vascular Cell Adhesion Molecule-1

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN).. In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN.. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Topics: Adiponectin; Adult; Biomarkers; Cross-Sectional Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Proteinuria; Risk Factors; Severity of Illness Index

This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone.

Topics: Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; E-Selectin; Endothelin-1; Enzyme Activation; Female; Intercellular Adhesion Molecule-1; Leptin; Peptidyl-Dipeptidase A; Pregnancy; Pregnancy Complications; Proteinuria; Rats; Rats, Sprague-Dawley; Xanthenes

Raised leptin levels have been reported in the placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unknown. This study investigates the effect of leptin administration on systolic blood pressure (SBP) and proteinuria and serum markers of endothelial activation during pregnancy in Sprague Dawley rats. From day 1 of pregnancy, 24 rats were randomised into those given either saline (group 1) or leptin at 60 or 120 μ g/kg/body weight/day (groups 2 and 3 resp.). SBP was measured every 5 days and 24-h urinary protein was measured at days 0 and 20 of pregnancy. Animals were euthanised on day 20 of pregnancy, and serum was collected for estimation of E-selectin and ICAM-1. Compared to group 1, SBP during the latter part of the pregnancy was significantly higher in the leptin-treated group (P < 0.01). Urinary protein excretion, serum E-selectin, and ICAM-1 were significantly higher in leptin-treated rats (P < 0.05). It seems that leptin administration to normotensive Sprague Dawley rats during pregnancy significantly increases SBP, urinary protein excretion, and markers of endothelial activation. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans.

Topics: Animals; Biomarkers; Blood Pressure; Body Weight; Drinking Behavior; E-Selectin; Endothelial Cells; Female; Intercellular Adhesion Molecule-1; Leptin; Pregnancy; Proteinuria; Rats; Rats, Sprague-Dawley; Systole

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Topics: Animals; Antibodies, Antinuclear; Biomarkers; Body Weight; Cytokines; Disease Models, Animal; Feeding Behavior; Female; Gene Expression Regulation; Humans; Insulin; Intra-Abdominal Fat; Leptin; Liver; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Proteinuria; TOR Serine-Threonine Kinases; Triglycerides

We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHRs) chronically treated with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (SHR-l). NG-nitro-L-arginine methyl ester (80 mg/L) administration for 3 weeks increased mean arterial pressure (MAP) from 196 ± 6 to 229 ± 3 mm Hg (P < 0.05). Treatment of SHR-l with Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7) (A779; 744 μg·kg(-1)·d(-1) ip) further elevated MAP to 253 ± 6 mm Hg (P < 0.05 vs SHR-l or SHR). Moreover, A779 treatment attenuated the reduction in MAP and proteinuria by either captopril (300 mg/L in drinking water) or hydralazine (1.5 mg·kg(-1)·d(-1) ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-l hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery after ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role in effectively buffering the increase in blood pressure and renal injury and the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage.

Topics: Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Brain; Captopril; Cytokines; Heart; Hydralazine; Hypertension; In Vitro Techniques; Insulin; Kidney; Leptin; Male; Myocardial Contraction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Peptide Fragments; Perfusion; Proteinuria; Rats; Rats, Inbred SHR; Ventricular Function, Left

Lipodystrophy is a rare disorder characterised by loss of adipose tissue, hypoleptinaemia, severe insulin resistance, diabetes and dyslipidaemia. The aims of this study were to determine whether leptin replacement in lipodystrophy patients ameliorates their metabolic abnormalities over an extended period of time and whether leptin therapy is effective in the different forms of lipodystrophy.. We conducted an open-label prospective study of patients with acquired forms of lipodystrophy and inherited forms of lipodystrophy secondary to mutations in the AGPAT2, SEIPIN (also known as BSCL2), LMNA and PPARgamma (also known as PPARG) genes. Between July 2000 and November 2008, 48 patients with lipodystrophy were treated with s.c. recombinant methionyl human leptin.. Serum triacylglycerol and HbA(1c) levels declined dramatically with leptin therapy. Among 35 patients with data at baseline and 12 months, serum triacylglycerol fell by 59% (from 10.18 +/- 2.67 mmol/l to 4.16 +/- 0.99 mmol/l [means +/- SE]; p = 0.008) and HbA(1c) decreased by 1.5 percentage points (from 8.4 +/- 0.3% to 6.9 +/- 0.3%; p < 0.001). A significant reduction was seen in total cholesterol and a trend towards reduction was observed in LDL-cholesterol at 12 months. HDL-cholesterol was unchanged. Among generalised lipodystrophy patients, proteinuria diminished with leptin replacement. Patients with both acquired and inherited forms of lipodystrophy experienced decreases in serum triacylglycerol and HbA(1c) levels.. Leptin replacement in lipodystrophy patients leads to significant and sustained improvements in glycaemic control and dyslipidaemia. Leptin is effective in the various forms of lipodystrophy, whether they are acquired or inherited, generalised or partial.. ClinicalTrials.gov ID NCT00025883. This work was supported by intramural research funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH).

Topics: Adipose Tissue; Adolescent; Adult; Aged; Child; Cholesterol; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Leptin; Lipodystrophy; Male; Middle Aged; Mutation; Prospective Studies; Proteinuria; Recombinant Proteins; Triglycerides

The present study tested a hypothesis that excess accumulation of sphingolipid, ceramide, its metabolites, or a combination contributes to the development of obesity and associated kidney damage. Liquid chromatography/mass spectrometry analysis demonstrated that C57BL/6J mice on the high-fat diet (HFD) had significantly increased plasma total ceramide levels compared with animals fed a low-fat diet (LFD). Treatment of mice with the acid sphingomyelinase (ASMase) inhibitor amitriptyline significantly attenuated the HFD-induced plasma ceramide levels. Corresponding to increase in plasma ceramide, the HFD significantly increased the body weight gain, plasma leptin concentration, urinary total protein and albumin excretion, glomerular damage index, and adipose tissue ASMase activity compared with the LFD-fed mice. These HFD-induced changes were also significantly attenuated by treatment of mice with amitriptyline. In addition, the decline of plasma glucose concentration after an intraperitoneal injection of insulin (0.15 U/kg b.wt.) was more sustained in mice on the HFD with amitriptyline than on the HFD alone. Intraperitoneal injection of glucose (3 g/kg b.wt.) resulted in a slow increase followed by a rapid decrease in the plasma glucose concentration in LFD and HFD plus amitriptyline-treated mice, but such blood glucose response was not observed in HFD-fed mice. Immunofluorescence analysis demonstrated a decrease in the podocin and an increase in the desmin in the glomeruli of HFD-fed mice compared with the LFD and HFD plus amitriptyline-treated mice. In conclusion, our results reveal a pivotal role for ceramide biosynthesis in obesity, metabolic syndrome, and associated kidney damage.

Topics: Adipose Tissue; Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Blood Pressure; Body Weight; Ceramides; Diet; Dietary Fats; Fluorescent Antibody Technique; Glucose Tolerance Test; Kidney; Kidney Diseases; Leptin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Proteinuria; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Mass, Electrospray Ionization; Sphingolipids; Sphingomyelin Phosphodiesterase

The Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat, a new model of obese type 2 diabetes, shows obesity, hyperglycemia, and hyperlipidemia from 6 weeks of age. Diabetic complications such as nephropathy and cataract are observed with aging; however, blood pressure change with age has not previously been examined. In this study, blood pressure was periodically measured and the change was investigated. Blood pressure in male SDT-fa/fa rats was elevated at 8, 16, and 24 weeks of age, whereas the heart rate was not changed. In addition to hyperglycemia, hyperlipidemia, and proteinuria, hyperleptinemia and increased urine angiotensinogen were observed in SDT-fa/fa rats. Blood pressure and heart rate in the male original SDT (SDT-+/+) rat did not significantly change. In conclusion, the SDT-fa/fa rat is a promising model, showing significant hypertension with diabetes mellitus.

Topics: Angiotensinogen; Animals; Blood Pressure; Diabetes Mellitus, Type 2; Disease Models, Animal; Heart Rate; Hyperglycemia; Hyperlipidemias; Hypertension; Leptin; Male; Obesity; Proteinuria; Rats; Rats, Sprague-Dawley

In earlier studies we found that a high-fat, high-energy diet (HFED) attenuates proteinuria, azotemia and lipid accumulation in the remnant kidney of rats subjected to 5/6 nephrectomy. This study was conducted to explore the mechanism of the salutary effect of HFED in association with moderate protein restriction in this model.. The 5/6 nephrectomized male rats were randomized to receive regular rat chow (CRF group, n = 6) or HFED diet (CRF + HFED, n = 7) for 12 weeks. Sham-operated rats served as controls (n = 6).. The CRF group exhibited azotemia, hypertension, proteinuria, diminished body weight, oxidative stress, glomerulosclerosis, tubulo-interstitial inflammation and upregulation of pro-oxidant [NAD(P)H oxidase], pro-inflammatory (NF-κB activation, increased MCP-1, lipoxygenase, ICAM-1, VCAM-1), pro-fibrotic (TGF-β, CTGF) and pro-apoptotic pathways (Bax, caspase-3) in the remnant kidney. Consumption of the HFED resulted in a 66% increment in lipid intake, 8% increment in carbohydrate intake and a 24% reduction in protein intake. The CRF + HFED group gained weight normally, had increments in leptin and adiponectin levels, and despite increments in plasma cholesterol and fatty acids, showed significant attenuation of oxidative stress, proteinuria and inflammation, and partial reversal of the remnant kidney upregulation of pro-oxidant, pro-inflammatory, pro-fibrotic and pro-apoptotic pathways.. Consumption of high-energy diet in association with mild protein restriction results in suppression of upregulated pathways that drive progression of renal injury in the remnant kidney model. These findings may have relevance in the management of chronic kidney disease in humans.

Topics: Adiponectin; Animals; bcl-2-Associated X Protein; Cachexia; Caspase 3; Creatinine; Diet, Protein-Restricted; Dietary Fats; Energy Intake; Inflammation; Leptin; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Oxidative Stress; Proteinuria; Rats; Thiobarbituric Acid Reactive Substances

Altered regulation of adiponectin and leptin may be relevant to endothelial dysfunction and cardiovascular complications in patients with chronic glomerulonephritis.. The relationship between the levels of plasma adiponectin, leptin and proteinuria, glomerular filtration rate and metabolic risk factors was investigated in 38 patients with chronic glomerulonephritis.. Plasma adiponectin was much higher in patients with heavy proteinuria (38.8 +/- 27.8 microg/mL) than in patients with mild proteinuria (13.3 +/- 5.1 microg/mL, P < 0.001) and with moderate proteinuria (18.1 +/- 8.0 microg/mL, P < 0.01). The levels of serum leptin were not changed among these groups. Proteinuria and lipoprotein(a) were a strong and direct correlate of plasma adiponectin (r = 0.75, P < 0.0001), while serum albumin and the glomerular filtration rate correlated inversely with this protein (r = -0.56, P = 0.0002; r = 0.38, P = 0.02). Body mass index and triglyceride were direct correlates (r = 0.37, P = 0.02 and r = 0.37, P = 0.02, respectively) of plasma leptin in patients with glomerulonephritis.. Plasma adiponectin but not plasma leptin levels correlate with proteinuria in patients with chronic glomerulonephritis.

Topics: Adiponectin; Adult; Aged; Chronic Disease; Female; Glomerulonephritis; Humans; Leptin; Male; Middle Aged; Proteinuria

The objective of this study was to evaluate the change in maternal serum leptin levels in preeclampsia and to study the relationship between maternal serum leptin and thyroid-stimulating hormone (TSH), body mass index (BMI), newborn weight, and proteinuria. Eighty-five pregnant women were included in this prospective study, of whom 50 were preeclamptic and 35 were normotensive. Maternal serum leptin levels were measured by the radioimmunoassay technique and TSH levels were measured by the electrochemiluminescence immunoassay method. The maternal serum leptin levels of preeclamptic and normotensive pregnant women were compared. In each group, the relationship between maternal serum leptin levels and TSH levels, BMI, newborn weight, and proteinuria was evaluated. The maternal serum leptin level was significantly higher in the preeclamptics than in the normotensive pregnant women. In the preeclamptic group, there was a strong positive correlation between maternal serum leptin levels and BMI (r =- 0.80; p < 0.001), a very weak positive correlation between maternal serum leptin levels and proteinuria (r = 0.305; p < 0.05), and a very weak inverse correlation between maternal serum leptin levels and birth weight (r = -0.377; p < 0.01). In the same group, there was no correlation between maternal serum leptin and serum TSH levels (r = 0.22; p > 0.05; Pearson correlation test). Leptin may be involved in the pathology of preeclampsia, and elevated maternal serum leptin levels may be a marker for the early stages of preeclampsia in pregnant women.

Topics: Adult; Body Mass Index; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Prospective Studies; Proteinuria; Thyrotropin

To determine serum leptin levels in hypertensive disorder of pregnancy.. In this prospective, cross-sectional, case control study, we measured serum leptin levels of 58 hypertensive pregnant women and 54 normal pregnant women. We also did blood and urine analysis for the evaluation of the severity of hypertensive disorder of pregnancy. The patients were followed until after delivery and information about labour was recorded. We analysed the difference and correlation between anthropometric measures, hormonal and biochemical parameters, and serum leptin levels in two groups.. In the study group, serum leptin levels were determined to be higher than the control group. Neonatal birth weight was significantly lower in the hypertensive group. While the serum uric acid, urea, aspartate aminotransferase, fibronectin, and fasting blood glucose levels were found to be higher, serum total protein and albumin levels were significantly lower among the hypertensive pregnant women. Hypertensive pregnant women were more insulin resistant. Serum leptin levels were highly and positively correlated with serum fibronectin, and C peptide levels. A negative significant correlation was observed between maternal serum leptin levels and neonatal birth weight among the pregnant women having the hypertensive disorders.. Serum leptin levels in hypertensive pregnant women appear to be higher. The determination of serum leptin levels may be as important as serum fibronectin and C peptide levels in the management of hypertensive disorder of pregnancy. C peptide and insulin may be due to hyperinsulinemia which leads to increased stimulation of leptin production by fatty tissue. Insulin resistance which appears in late pregnancy is more significant especially in pregnancies complicated by preeclampsia.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cross-Sectional Studies; Female; Fibronectins; Humans; Hypertension, Pregnancy-Induced; Insulin Resistance; Leptin; Logistic Models; Pregnancy; Prospective Studies; Proteinuria; Skinfold Thickness

Data regarding the effectiveness of chronic exercise training in improving survival in patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine the effect of exercise training on survival in a well-defined animal model of heart failure (HF), using the lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present with decompensated, dilated HF between approximately 18 and 23 mo of age. SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of age. Exercise training consisted of 6 mo of low-intensity treadmill running. Exercise training delayed the onset of overt HF and improved survival (P < 0.01), independent of any effects on the hypertensive status of the rats. Training delayed the myosin heavy chain (MyHC) isoform shift from alpha- to beta-MyHC that was seen in sedentary animals that developed HF. Exercise was associated with a concurrent increase in cardiomyocyte length (approximately 6%), width, and area and prevented the increase in the length-to-width ratio seen in sedentary animals in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum leptin levels observed in rats with HF were suppressed by low-intensity exercise training. No significant alterations in sarco(endo)plasmic reticulum Ca2+ ATPase, phospholamban, or Na+/Ca2+ exchanger protein expression were found in response to training. Our results indicate that 6 mo of low-intensity exercise training delays the onset of decompensated HF and improves survival in the male SHHF rat. Similarly, exercise intervention prevented or suppressed alterations in several key variables that normally occur with the development of overt CHF. These data support the idea that exercise may be a useful and inexpensive intervention in the treatment of HF.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Western; Calcium; Cell Separation; Cell Size; Citrate (si)-Synthase; Heart Failure; Isomerism; Leptin; Male; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Survival Analysis

Leptin has direct and indirect effects on renal pathophysiological characteristics. In the present study, the effects of long-term leptin infusion on the renal hemodynamics, renal excretory functions, and the expression of transforming growth factor-beta (TGF-beta), plasma endothelin-1 (ET-1) levels, and preventive effects of the angiotensin II type 1 receptor antagonist, losartan, on these renal changes were evaluated.. The study was performed by using forty Wistar albino rats. On day 0, osmotic mini-pumps filled with leptin or placebo were intraperitoneally placed under sterile conditions. The rats in Group L (Leptin group, n=15) and Group LL (Leptin-losartan group, n=15) were given recombinant murine leptin at a rate of 250 ng per hour for 28 days. Control rats (Group C, n=10) were administered placebo at the same infusion rate. The rats in Group LL were also administered losartan (10 mg kg(-1) d(-1)) perorally for 28 days. On day 28, the rats were placed in metabolic cages, and the food and water intakes were determined, and the urine was collected for 24 h. At the end of the study, systolic blood pressure (SBP), diastolic blood pressure (DBP) were determined directly from the left femoral artery, and renal blood flow (RBF) was recorded indirectly using a laser Doppler flow module.. Leptin infusion did not produce any changes in systemic arterial blood pressures and urinary flow rate. The rates of creatinine (Cr), sodium (Na), and protein excretions of the animals infused leptin were significantly increased. The urinary Cr and Na excretions were decreased, while the urinary protein excretion was normalized with the losartan treatment. The rats infused leptin had also higher circulating ET-1 levels. ET-1 levels were also reversed to the normal values with the losartan treatment. Renal TGF-beta1 expression was determined immunohistochemically, and it was more prominent in the renal tubules from the rats treated with leptin. The losartan treatment had no effect on renal TGF-beta1 expression.. Our results indicate that pathophysiological increases in plasma leptin concentrations cause enhanced renal Na, Cr and protein excretions, and high circulating ET-1 levels. Na and Cr excretions were decreased, while proteinuria and plasma ET-1 levels were normalized by losartan treatment, suggesting that renin-angiotensin system activation may have a role in leptin induced renal changes. TGF-beta1 may have an important role in leptin induced nephropathy.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Blood Pressure; Creatinine; Kidney; Kidney Diseases; Leptin; Losartan; Proteinuria; Rats; Rats, Wistar; Renin-Angiotensin System; Sodium; Transforming Growth Factor beta; Transforming Growth Factor beta1; Urination

Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration.

Topics: Adolescent; Adult; Aged; Biopsy; Child; Creatinine; Diabetic Nephropathies; Female; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Kidney Diseases; Leptin; Lipodystrophy; Male; Middle Aged; Proteinuria; Recombinant Proteins; Syndrome

Leptin may contribute to renal pathology in some situations by stimulating transforming growth factor-beta1 (TGF-beta1) synthesis. The soluble leptin receptor (sOb-R) is a transport protein contributing to binding and activation of circulating leptin. We investigated the interaction between serum and urinary leptin, TGF-beta1, and serum sOb-R levels in 38 patients with minimal change nephrotic syndrome (MCNS) aged between 6 and 12 years and 10 age- and sex-matched healthy controls (group III). Patients were divided into two groups: group I, proteinuria exceeding >40 mg/m(2) per hour and group II, patients in remission. Serum leptin levels in group I were significantly lower than those in group II and group III ( P=0.011, P=0.007, respectively). There was a negative correlation between serum leptin levels and proteinuria ( r=-0.52, P=0.02) as well as between serum leptin and sOb-R levels ( r=-0.82, P=0.000) in group I. Urine leptin and sOb-R levels in group I were significantly higher than in group II ( P=0.0021, P=0.001, respectively) and group III ( P=0.07, P=0.009, respectively). Serum TGF-beta1 levels in healthy controls (406+/-424 pg/ml) were significantly lower than those in groups I and II ( P=0.004, P=0.000, respectively). However, no significant correlation was found between the serum TGF-beta1 and leptin levels in MCNS patients. In conclusion, low serum leptin, high serum TGF-beta1 and sOb-R levels, and elevated urine leptin concentrations were observed at the onset of MCNS. Since long-term proteinuria and leptinuria might be associated with the progression of renal damage, future in vivo and in vitro studies are needed to explain the interaction between these parameters in different types of nephrotic syndrome.

Topics: Body Mass Index; Child, Preschool; Female; Humans; Infant; Leptin; Male; Nephrosis, Lipoid; Proteinuria; Receptors, Cell Surface; Receptors, Leptin; Solubility; Transforming Growth Factor beta; Transforming Growth Factor beta1

In patients with nephrotic syndrome, severe proteinuria is related to significant leptinuria; serum leptin levels remain unchanged. The goal of this study was to elucidate the role of the soluble leptin receptor (sOB-R) in maintaining serum leptin levels in nephrotic patients. Patients with proteinuria were compared with patients in remission of nephrotic syndrome. In this group proteinuria did not exceed 100 mg/m(2) of body surface area per day. The period of remission was at least 6 months and was equal in all patients included. The sOB-R level (mean +/- SD) in serum of patients with nephrotic syndrome was significantly higher during proteinuria (61.0 +/- 17.8 ng/ml) than those in remission or in control patients (36.7 +/- 7.0 ng/ml, 36.6 +/- 12.0 ng/ml, respectively, P < 0.0001). The ratio between serum leptin levels and the sOB-R (free leptin index) was significantly lower in the proteinuric group (0.012 +/- 0.005 vs. 0.06 +/- 0.03 and 0.07 +/- 0.03 in remission and control group, respectively) (P < 0.001). Urinary sOB-R excretion was similar in all groups. Our data suggest that the counteracting pathway in case of leptin loss in parallel to severe proteinuria in nephrotic syndrome is the up-regulation of its soluble binding protein in serum, which can keep total serum leptin levels constant.

Topics: Adolescent; Child; Female; Humans; Leptin; Male; Nephrotic Syndrome; Proteinuria; Receptors, Cell Surface; Receptors, Leptin; Solubility; Up-Regulation

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Composition; Body Weight; Diet; Fructose; Glomerulosclerosis, Focal Segmental; Hypertension; Kidney Glomerulus; Leptin; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Organ Size; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Thiazepines

Nephrotic syndrome (NS) remains a serious clinical setting characterized by marked proteinuria, hypoproteinemia and hypercholesterolemia, usually accompanied by the presence of oedemas. It could be presumed, that the newly discovered hormone leptin plays an important role in the complex metabolic processes occurring in patients with NS, in which apart from the changes in the hydratation, and the protein and lipid spectre profile changes, the alteration of the metabolism of glycides elicited by the treatment with corticosteroids (CS) is often observed. The aim of the study was to investigate the plasma levels of leptin and its plasma soluble receptor (sLe-R) before and after the treatment with CS and to evaluate their relationship with albuminemia and/or proteinuria. The study group consisted of 15 men and 15 women (mean age 49 +/- 13.7 years) with newly diagnosed NS, verified by renal biopsy, in which subsequently CS treatment was started. Before the treatment (period 1) and further one month (period 2) and six months (period 3) after the start of the treatment the following parameters were measured: body mass index (BMI), serum levels of creatinine, albumin, cholesterol, triglyceride, cholinesterase, proteinuria/24 hour and plasma levels of leptin and sLe-R. In comparison to the relatively high values of BMI in the period 1 a decrease of BMI towards the physiologic range was observed during the treatment periods. Statistically significant changes were also observed in proteinuria (decrease) and in serum cholesterol and albumin levels of whereas in other biochemical parameters, including plasma leptin and sLe-R levels, statistically significant changes were not found. A trend to negative correlation with borderline statistical significance could be observed between leptin and sLe-R. The results of our relatively unique study on leptin--dealing with long-term follow-up of the patients with NS suggest that regardless prominent metabolic alterations present in NS the plasma levels of leptin and sLe-R remain relatively stable, and that of regulation of leptin in this setting is probably complex and multifactorial.

Topics: Adolescent; Adult; Aged; Female; Glucocorticoids; Humans; Leptin; Male; Middle Aged; Nephrotic Syndrome; Proteinuria; Receptors, Cell Surface; Receptors, Leptin; Serum Albumin

Comparative studies have shown that Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a nearly complete metabolic syndrome with obesity, moderate hypertension, dyslipidemia, hyperinsulinemia, and impaired glucose tolerance up to an age of 28 weeks. Because metabolic data thereafter are missing, WOKW and disease-resistant DA rats were studied for 12 months beginning at an age of 5 months.. Eighteen male inbred WOKW and DA rats were studied monthly from the 5th to the 17th month of life for traits of the metabolic syndrome such as body weight, body mass index (BMI), serum triglycerides, total cholesterol, leptin, insulin as well as glucose tolerance, 24 h excretion of urine total protein and creatinine including telemetric measurement of blood pressure in six males per each group.. Except for serum total cholesterol, the measured values for most traits studied were significantly higher in WOKW than in DA rats at an age of 5 months. At an age of 17 months all traits were significantly elevated in WOKW compared with DA rats. WOKW rats were hypertensive, dyslipidemic, obese, glucose intolerant, hyperinsulinemic and proteinuric.. Considering the phenotype of the WOKW rat described until now and the fact that the metabolic syndrome in this rat is polygenetically determined, the WOKW rat is the most suitable animal model to study the pathophysiology of the facets of the syndrome.

Topics: Aging; Animals; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Creatinine; Glucose Tolerance Test; Insulin; Leptin; Male; Metabolic Syndrome; Proteinuria; Rats; Triglycerides

Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity-linked glomerular injury.. At 6 weeks of age obese Zucker rats were either fed ad libitum or were restricted in food intake at various ages (6, 12, 26, or 50 weeks) to that consumed by lean Zucker rats (14 g/day). Every four weeks 24-hour urine collections, blood pressure, and venous blood samples were obtained until the end of study (60 weeks).. Food restriction at 6 or 12 weeks of age prevented glomerular injury and hypertrophy and delayed the development of hypertension, hypercholesterolemia, and hyperinsulinemia. Food restriction at 26 weeks of age reduced proteinuria, while restriction at 50 weeks prevented further increases in proteinuria without altering pre-existing hypercholesterolemia, hypertension, or hyperinsulinemia. Hypertriglyceridemia and glomerular hyperfiltration in the obese animals were reversed at any age by food restriction. Plasma leptin levels were elevated in all obese groups.. (1) Early food restriction provided the greatest metabolic and renal benefits; (2) glomerular injury correlated with hyperphagia-induced hyperfiltration and hypertriglyceridemia and both were prevented by food restriction; (3) hypercholesterolemia was due to an increase in LDL and/or VLDL cholesterol; and (4) leptin does not directly contribute to glomerular injury in the obese Zucker rat.

Topics: Age Factors; Animals; Blood Pressure; Body Weight; Eating; Female; Glomerular Filtration Rate; Insulin; Kidney Diseases; Kidney Glomerulus; Leptin; Lipoproteins, LDL; Lipoproteins, VLDL; Obesity; Organ Size; Proteinuria; Rats; Rats, Zucker; Renal Circulation

Topics: Glomerulosclerosis, Focal Segmental; Humans; Incidence; Kidney Diseases; Leptin; Obesity; Proteinuria

In humans, short term changes of serum leptin lead to alterations in food intake and energy expenditure. The objective of the present study was to relate urine leptin concentrations with the extent of proteinuria in patients with nephrotic syndrome (NS). A second goal was to investigate the impact of potential urinary leptin losses on serum leptin concentrations and body composition.. Seventeen patients with proteinuria were compared with twenty patients with remission of NS and ten healthy children. Leptin was measured by radioimmunoassay.. Urinary leptin excretion in proteinuric patients was significantly higher than in non-proteinuric patients with and without NS and in healthy controls (2.64+/-0.034 microg/g creatinine, 0.026+/-0.05 microg/g creatinine, and 0.073+/-0.11 microg/g creatinine respectively; P<0.001 and P<0.01 respectively compared with controls). Urine leptin positively correlated with urine IgG concentration (P=0.013, r2=0.36) in the proteinuric group. No difference in serum leptin values could be demonstrated between the three groups.. In summary, our data demonstrate a significant leptin excretion in children with severe proteinuria. Proteinuria, however, does not lead to changes in serum leptin, suggesting that the significant loss of leptin is compensated for by sustained up-regulation of leptin production.

Topics: Adolescent; Body Mass Index; Child; Female; Humans; Leptin; Male; Nephrotic Syndrome; Proteinuria; Skinfold Thickness

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann-Whitney U test. The correlation between leptin and gender was computed using the product-moment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

Topics: Adult; Antihypertensive Agents; Birth Weight; Female; Fetal Blood; Gestational Age; Humans; Hypertension; Infant, Newborn; Labetalol; Leptin; Magnesium; Male; Multivariate Analysis; Pre-Eclampsia; Pregnancy; Proteinuria; Regression Analysis; Sex Factors