leptin and Acidosis

Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.

Topics: Acidosis; Amino Acids, Branched-Chain; Animals; Firefly Luciferin; Humans; Hydrocortisone; Hyperparathyroidism, Secondary; Insulin Resistance; Kidney Failure, Chronic; Leptin; Luciferases; Nutritional Status; Rats

Hyperleptinemia and metabolic acidosis (MA) are frequently observed in patients on hemodialysis (HD). While the role of leptin in patients on HD is not completely understood, HD only partially corrects MA. Both leptin and acidosis have effect on bone disease. The goal of the present study was to evaluate the effects of MA correction on chronic kidney disease-mineral and bone disorder laboratory parameters and leptin levels.. Forty-eight patients on HD, aged 43±19 years, were prospectively studied. Individual adjustments in the bicarbonate dialysate concentration were made to maintain pre-dialysis concentration≥22 mEq/l. Blood gas analysis was done monthly for 4 months (M1-M4).. From M0 to M4, serum albumin increased (from 3.5 ±0.3 to 4.0±0.3 g/l, p<0.0001) while β2 microglobulin decreased (from 27.6±8.3 to 25.8±6.8 µg/ml, p=0.025). Serum leptin decreased in all but three patients, as well as leptin/adiponectin ratio (p<0.0001). There was a decrease in ionized serum calcium (from 5.0±0.5 to 4.7±0.5 mg/dl, p =0.002) and an increase in parathyroid hormone (PTH) [from 191 (85, 459) to 446 pg/ml (212, 983), p<0.0001] and in serum phosphate (from 5.4±1.4 to 5.8±1.1 mg/dl, p=0.048).. MA correction in HD patients can decrease leptin, an atherogenic marker. The impact of such treatment extends to uremic bone disease, as decrease in serum calcium and increase in PTH. However, this could be an undesirable effect because it may aggravate a secondary hyperparathyroidism. Whether the reduction in leptin levels has impact on outcomes in patients on hemodialysis deserves further investigation.

Topics: Acidosis; Adiponectin; Adult; beta 2-Microglobulin; Bicarbonates; Blood Gas Analysis; Calcium; Dialysis Solutions; Female; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Parathyroid Hormone; Phosphates; Prospective Studies; Renal Dialysis; Serum Albumin; Sex Factors; Young Adult

The mechanism underlying the decline in milk quality during periods of feeding high-concentrate diets to dairy ruminants is not well documented. The aim of this study was to investigate the metabolic changes in the liver that contribute to the input of substrate precursors to the mammary gland after feeding a high-concentrate diet to lactating goats for a long period.. Eight mid-lactating goats with rumen cannulas were randomly assigned to two groups. For 9 weeks, the treatment group was fed a high-concentrate diet (60% concentrate of dry matter, HC) and the control group was fed a low-concentrate diet (40% concentrate of dry matter, LC). Ruminal fluid, plasma, and liver tissues were sampled, microarray techniques and real-time polymerase chain reaction were used to evaluate metabolic parameters and gene expression in liver.. Feeding a 60%-concentrate diet for 9 weeks resulted in a significant decrease in rumen pH. Changes in fat and protein content also occurred, which negatively affected milk quality. Plasma levels of leptin (p = 0.058), non-esterified fatty acid (p = 0.071), and glucose (p = 0.014) increased markedly in HC group. Plasma cortisol concentration was significantly elevated in the treatment group (p<0.05). Expression of the glucocorticoid receptor protein gene was significantly down-regulated (p<0.05) in the liver. The expression of genes for interleukin 1β, serum amyloid A, C-reactive protein, and haptoglobin mRNA was significantly increased (p<0.05) in the HC group. GeneRelNet analysis showed that gene expression involved in inflammatory responses and the metabolism of lipids, protein, and carbohydrate were significantly altered by feeding a high-concentrate diet for 9 weeks.. Activation of the acute phase response and the inflammatory response may contribute to nutrient partitioning and re-distribution of energy in the liver, and ultimately lead to a decline in milk quality.

Topics: Acidosis; Animal Feed; Animals; Blood Glucose; C-Reactive Protein; Diet; Fatty Acids; Female; Gene Expression; Goats; Haptoglobins; Interleukin-1beta; Lactation; Leptin; Liver; Milk; Rumen; Serum Amyloid A Protein

Metabolic acidosis, a common feature of uremia, has a well documented wasting effect on skeletal muscle. In contrast, the effect of metabolic acidosis on adipose tissue is unknown. Serum levels of the adipocyte hormone leptin have been shown to be lower in acidotic uremic rats when compared with uremic controls. This study investigated the effect of acidosis on leptin protein secretion and leptin gene expression. This was studied in vitro by means of 3T3-L1 cultured adipocytes. Leptin secretion was decreased at an acid pH of 7.1 compared with a control pH of 7.5 (1277 versus 1950 pg/well/48 h, P < 0.05). In contrast, acidosis did not affect leptin mRNA content. Glucose transport was reduced by 39% at pH 7.1 at 24 h, which was comparable in magnitude with the inhibition of leptin secretion at the same pH. The glucose transport inhibitors cytochalasin B (0.5 to 50 micro M) and phloretin (0.05 to 0.25 mM) mimicked the effect of acidosis and reduced leptin secretion in a dose-dependent fashion (P < 0.02). Dose-response curves for the inhibition of glucose uptake showed that decreasing glucose transport to the same extent as with acid was sufficient to drive down leptin secretion, independently of changes of leptin mRNA. Acid decreases leptin secretion from 3T3-L1 adipocytes through a post-transcriptional mechanism via changes in glucose transport. This starvation-like response may be physiologically important in conditions such as uremia to prevent excessive energy expenditure.

Topics: 3T3 Cells; Acidosis; Adipocytes; Animals; Biological Transport; Down-Regulation; Glucose; Hydrogen-Ion Concentration; Leptin; Mice; RNA Processing, Post-Transcriptional; RNA, Messenger; Transcription, Genetic

Patients with chronic renal failure are frequently characterized by malnutrition, hyperleptinaemia and metabolic acidosis. Both hyperleptinaemia and chronic metabolic acidosis are presumed to contribute to the pathogenesis of malnutrition observed in this group of patients. It has been reported, that in vitro adipocytes exposed to acidotic medium decrease leptin secretion. The aim of present study was to analyze the possible impact of uraemic metabolic acidosis on leptinaemia in haemodialysis patients with chronic renal failure. - 94 haemodialysed patients (58 M, 36 F; mean age 45 +/- 1 years) were enrolled in this study. 56 patients were on haemodialysis treatment for one year using an acetate dialysis fluid, while 38 patients were haemodialysed at least for 3 months with a dialysate buffered with bicarbonate. Plasma leptin concentration, blood gases and body composition were assessed in all examined subjects. - Patients haemodialysed with an acetate and bicarbonate buffered dialysate did not differ with respect to body weight, body mass index (BMI), total fat mass (TFM) and plasma leptin concentration. Patients haemodialysed with an acetate buffered dialysate were characterized by a significantly more severe metabolic acidosis than patients on bicarbonate haemodialysis. Patients were divided according to the actual hydrogen ion concentration: over 60 nmol/l, 45-60 nmol/l and below 45 nmol/l. These subgroups did not differ significantly by body weight, BMI and TFM. Only a slightly (not significantly), lower median leptinaemia was found in patients with elevated hydrogen ion concentration. No significant correlation was noticed between blood hydrogen or hydrocarbonate ion concentration respectively and logarithmic values of plasma leptin concentration (tau = 0.025, p = 0.72; tau = - 0.021, p = 0.76 respectively). - From results obtained in this study we may conclude that, blood hydrogen ion concentration does not influence substantially or only moderately to plasma leptin concentration in haemodialysed patients.

Topics: Acidosis; Bicarbonates; Body Composition; Female; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Statistics, Nonparametric

To examine the relationship between serum leptin levels (SLL) and metabolic acidosis in patients with chronic renal failure (CRF).. SLL in control patients and in predialysis patients with CRF were measured and compared. SLL before and after correction of acidosis in patients with CRF were also compared.. Twenty-five patients with CRF (10 men and 15 women) aged 51.2 +/- 10.4 years and control patients (healthy subjects, 23 men and 25 women) aged 42.1 +/- 12.6 years were studied.. Five percent sodium bicarbonate (NaHCO(3), 2 to 3 mL/kg) was intravenously infused on the morning of the first day of treatment. NaHCO(3) was taken orally at a dosage of 50 to 200 mg/kg/d for 3 to 5 days thereafter.. SLL before and after NaHCO(3) treatment was measured by radioimmunoassay, and blood gas was measured before and after correction of metabolic acidosis in patients with CRF.. SLL in the normal control group (n = 48) was 10.04 +/- 7.0 ng/mL and was realated to body mass index (BMI) (P =.0331). SLL in men (n = 23) was lower than that in female controls (n = 25, P <.01). SLL in patients with CRF (n = 25) before (plasma HCO(3)(-), 13.03 +/- 3.05 mmol/L) and immediately after improvement of metabolic acidosis (plasma HCO(3)(-), 18.35 +/- 4.21 mmol/L) was 14.52 +/- 9.27 ng/mL and 15.34 +/- 11.89 ng/mL (P >.05), respectively. SLL measured 3 to 5 days after treatment for metabolic acidosis (plasma HCO(3)(-), 20.46 +/- 4.03 mmol/L) was 19.33 +/- 14.58 ng/mL, which was significantly higher than that in the normal control group and that in acidotic patients before NaHCO(3) treatment (P <.01).. SLL in acidotic patients with CRF were comparable to that in control subjects, and SLL was significantly increased after correction of metabolic acidosis in patients with CRF. The preliminary results suggest that hyperleptinemia in patients with CRF may be masked by metabolic acidosis and that metabolic acidosis may inhibit leptin synthesis or secretion. Further studies are needed to clarify the mechanisms.

Topics: Acidosis; Administration, Oral; Adult; Aged; Blood Gas Analysis; Body Mass Index; Case-Control Studies; Female; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Radioimmunoassay; Sex Factors; Sodium Bicarbonate

Marked hyperleptinaemia and metabolic acidosis are common findings in patients with chronic renal failure. In animal models, both leptin administration and acidosis reduce food intake. However, leptin causes loss of body fat, while acidosis induces muscle wasting. Whether a low pH and leptin production are related has not been studied. Leptin secretion was measured in cultured 3T3-L1 adipocytes exposed to acid or control pH for up to 96 h. In addition, serum leptin was compared between acidotic and bicarbonate-treated uraemic Wistar rats using the remnant model. Leptin levels in the culture medium were decreased at an acid pH of 7.1 compared with a control pH of 7.5 at 96 h (562+/-78 and 831+/-103 pg.48 h(-1). well(-1) respectively; mean+/-S.E.M.; P=0.037). Similarly, serum leptin in uraemic rats was found to be lower in the acidotic group than in the bicarbonate-treated group, although this observation fell just short of statistical significance (1273+/-171 compared with 2059+/-376 pg/ml; P=0.07). In conclusion, acidosis decreases leptin secretion from cultured adipocytes. Accordingly, acidotic uraemic rats seem to exhibit lower serum leptin levels than their bicarbonate-supplemented counterparts. This study is the first report providing a link between acidosis and leptin levels.

Topics: 3T3 Cells; Acidosis; Adipocytes; Animals; Female; Hydrogen-Ion Concentration; Leptin; Mice; Rats; Rats, Wistar; Uremia