leptin and Acquired-Immunodeficiency-Syndrome

Both overnutrition and undernutrition affect energy metabolism, with overnutrition raising energy expenditure and undernutrition lowering it. Fever is a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS, diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is increased or decreased often depends on how advanced the disorder is. Early on, when the greater protein turnover characteristic of these conditions is paramount, energy expenditure is increased. In addition, in diseases such as cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the cytokines' thermogenic effect initially increases the metabolic rate. However, as the disease becomes more advanced and leads to cachexia, energy expenditure drops below normal. Acute conditions such as burns and trauma significantly raise energy expenditure, primarily by increasing sympathetic response and the release of catecholamines, which are powerful stimulators of energy expenditure.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Aged; Arthritis, Rheumatoid; Basal Metabolism; Burns; Diabetes Mellitus; Eating; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Neoplasms; Obesity; Wounds and Injuries

Leptin is an adipocyte secreted hormone and an important regulator of neuroendocrine, metabolic, and immune function. Both r-metHuLeptin and IGF1 administration result in reduced central adipose tissue in subjects with highly active antiretroviral therapy-induced metabolic syndrome (HAART-MS) but whether the effects of leptin are mediated through increasing IGF levels remains unknown.. To assess whether r-metHuLeptin improves the HAART-MS by regulating circulating IGF and IGFBPs, we first conducted a cross-sectional study of 118 men and women with HIV infection and >6 months of exposure to antiretroviral medications to examine any association between circulating IGF1 and leptin levels. We also performed a randomized, double-blinded, placebo-controlled, crossover trial of recombinant human leptin (r-metHuLeptin) administration to seven HIV positive men with lipoatrophy and leptin deficiency (leptin <3 ng/ml) related to antiretroviral medication use.. In the observational study, leptin levels were inversely associated with circulating IGF1 levels after adjusting for age and gender (r=0.27 P=0.002), but this inverse association became non-significant after adjustment for % body fat and exercise. In the interventional leptin study, leptin levels increased significantly during r-metHuLeptin treatment (from 1.34+/-0.20 ng/ml at baseline to 17+/-5.05 ng/ml after 8 weeks P=0.046) and metabolic parameters improved including reduced fasting insulin levels and reduced homeostasis model assessment-insulin resistance (HOMA-IR). Despite the increase in circulating leptin levels, there was no change in IGF1, IGF2, free IGF1, or IGF-binding proteins during the 2-month treatment period.. The effects of r-metHuLeptin in patients with HAART-MS are not mediated through increasing IGF or IGFBP levels.

Topics: Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Antiretroviral Therapy, Highly Active; Cross-Over Studies; Cross-Sectional Studies; Drug Therapy, Combination; Female; HIV-1; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Middle Aged; Placebos

Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART).. This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor.. Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1 (Rho = 0.334; p= 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α, CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009).. We showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART.

Topics: Acquired Immunodeficiency Syndrome; Adult; Biomarkers; Blood Glucose; Case-Control Studies; Female; Ferritins; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Plasminogen Activator Inhibitor 1

Topics: Acquired Immunodeficiency Syndrome; Animal Rights; Compassionate Use Trials; Coronary Artery Bypass; Dietary Sucrose; Drug and Narcotic Control; Drug Carriers; Drug Industry; Global Health; Health Policy; Humans; Leptin; Lipodystrophy; Malaria; Nonprescription Drugs; Tuberculosis; World Health Organization

Higher body mass index (BMI) is associated with increased serum C-reactive protein (CRP) levels in HIV-infected individuals on antiretroviral therapy (ART), but the relationship of adipose tissue mass to systemic inflammation is not well described in this population. We hypothesized that serum adipokine levels (i.e., hormones produced by adipocytes) are a superior predictor of CRP compared to anthropometric or radiographic measures of body composition in patients on effective, stable ART. We evaluated the relationship of serum leptin, adiponectin, and resistin, BMI, and dual energy x-ray absorptiometry (DEXA) measurements with serum highly sensitive CRP (hsCRP) in a cross-sectional cohort of 106 predominantly virologically suppressed, HIV-infected adults on ART for ≥24 weeks using multivariable linear regression and formal criteria to assess statistical mediation. Median BMI, hsCRP, and leptin values were 25.2 kg/m(2), 3.0 mg/liter, and 3.8 ng/ml, respectively. BMI and DEXA limb fat, body fat, and trunk fat measurements were significantly associated with both serum leptin and hsCRP levels (all p≤0.02). Leptin was also associated with hsCRP (p<0.01). The regression coefficient for the effect of BMI or DEXA measurements on hsCRP was reduced, and the relationship was no longer statistically significant, after adjusting for leptin, indicating leptin functioned as a mediating variable within these relationships. Adiponectin and resistin levels did not demonstrate similar effects. Serum leptin was a superior predictor of hsCRP compared to BMI and DEXA body fat measurements, which may reflect alterations in body composition in treated HIV infection and the important contribution of adipose tissue to inflammation in this population.

Topics: Absorptiometry, Photon; Acquired Immunodeficiency Syndrome; Adiponectin; Adipose Tissue; Adult; Anti-HIV Agents; Body Composition; Body Mass Index; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Predictive Value of Tests

To investigate the prevalence of glucose and lipid abnormalities in AIDS patients treated with highly active antiretroviral therapy (HAART) and difference thereof between the HIV-lipodystrophy (LD) and non-HIV-LD groups, and to compare the plasma levels of adiponectin (APN) and leptin (LEP) and their relationship to metabolic disturbance and fat redistribution in these 2 groups.. Fifty-two HIV-infected patients were divided into HIV-LD group and non-HIV-LD group according to the patients' reports and doctors' evaluation. Body composition was assessed by whole body dual-energy X-ray absorptiometry. Plasma samples were analyzed for cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, APN, and LEP. The prevalence of dyslipidemia and hyperinsulinemia, the difference of adipocytokine levels, and the relationship of adiponectin, leptin with lipids, insulin as well as fat mass in different body regions were analyzed between the groups.. The prevalence rates of hypercholesterolaemia, hypertriglyceridaemia, and low HDL-C level were 17.3%, 50.0%, and 17.3% respectively. The rate of hyperinsulinemia and any kind of dyslipidemia were 25.0% and 59.6%. Compared with non-HIV-LD patients, HIV-LD patients had higher TG level, and lower HDL-C and APN levels. In the HIV-LD group, the APN level was correlated positively with limb/total body fat, but negatively with trunk/total body fat, and was an independent predictor of HDL-C and insulin level. However, LEP was positively correlated with the levels of total body fat, limb fat, and trunk fat in both groups.. The prevalence rates of dyslipidemia and insulin resistance are high in Chinese HIV/AIDS patients receiving HAART, especially in the HIV-LD group. The APN concentration in the HIV-LD patients is closely related to fat redistribution and independently predicts the levels of HDL-C and insulin. LEP can serve as a biomarker of total body fat mass.

Topics: Acquired Immunodeficiency Syndrome; Adiponectin; Adult; Aged; Antiretroviral Therapy, Highly Active; Female; Humans; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Lipids; Lipodystrophy; Male; Middle Aged

Highly active antiretroviral therapy (HAART) has significantly improved the prognosis of HIV(+) in children. Human immunodeficiency-associated lipodystrophy syndrome (HALS) is a side effect of HAART seen predominantly in adults and less often in children. Leptin is a protein thought to play an important role in body composition and has been shown to have immunomodulatory effects. We retrospectively studied serum levels of leptin in a cohort of eight HIV-infected children followed prospectively before and during HAART and investigated whether there is a correlation of these levels with the clinical, immunological, viral or nutritional changes observed during treatment in these children. None of our children developed HALS. In this small cohort of children, we found that serum leptin levels were appropriate to the nutritional status of the patient and that leptin/BMI increased in patients who responded to HAART. In conclusion, in HIV(+) children during HAART, leptin levels are related to the nutritional status of the child.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cohort Studies; Female; HIV; HIV-Associated Lipodystrophy Syndrome; Humans; Infant; Leptin; Male; Nutritional Status; Retrospective Studies; Statistics, Nonparametric; Viral Load

Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin.. The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy.. We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months.. Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured.. Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected.. r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antiretroviral Therapy, Highly Active; Body Composition; Body Mass Index; Cross-Over Studies; Double-Blind Method; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Lipids; Lipoproteins, HDL; Male; Metabolic Syndrome; Placebos; Recombinant Proteins

Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.

Topics: Acquired Immunodeficiency Syndrome; Adiponectin; Adolescent; Blood Glucose; Child; Child, Preschool; Dyslipidemias; Early Diagnosis; Female; HIV-Associated Lipodystrophy Syndrome; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male

HIV protease inhibitor-related lipodystrophy is characterized by peripheral fat loss, hyperlipidemia, and insulin resistance. Increased availability of lipid to muscle may be one of the mechanisms that induce insulin resistance. Regional fat, intramyocellular lipid (by (1)H-magnetic resonance spectroscopy), serum lipids, and insulin-stimulated glucose disposal (by hyperinsulinemic-euglycemic clamp) were quantified in 10 men who had HIV-1 infection with moderate to severe lipodystrophy and a control group of 10 nonlipodystrophic men who had HIV-1 infection and were naïve to protease inhibitors to examine the effects of lipodystrophy on glucose and lipid metabolism. Lipodystrophic subjects showed lower insulin-stimulated glucose disposal than control subjects (P = 0.001) and had increased serum triglycerides (P = 0.03), less limb fat (P = 0.02), increased visceral fat as a proportion of total abdominal fat (P = 0.003), and increased intramyocellular lipid (1.90 +/- 0.15 vs. 1.23 +/- 0.16% of water resonance peak area; P = 0.007). In both groups combined, visceral fat related strongly to intramyocellular lipid (r = 0.83, P < 0.0001) and intramyocellular lipid related negatively to insulin-stimulated glucose disposal (r = -0.71, P = 0.0005). Fasting serum cholesterol and triglycerides related positively to intramyocellular lipid and visceral fat in lipodystrophic subjects only. The data indicate that lipodystrophy is associated with increased lipid content in muscle accompanying impaired insulin action. The results do not establish causation but emphasize the interrelationships among visceral fat, myocyte lipid, and insulin action.

Topics: Absorptiometry, Photon; Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Anti-HIV Agents; Blood Glucose; Body Composition; HIV Protease Inhibitors; Homeostasis; Humans; Indinavir; Insulin; Leptin; Lipids; Lipodystrophy; Magnetic Resonance Imaging; Male; Middle Aged; Nelfinavir; Ritonavir; Saquinavir

1. Leptin inhibits food intake and is an important regulator of long-term energy balance. In rodents, plasma concentrations of leptin are increased by administration of interleukin-1 and tumour necrosis factor. Hyperleptinaemia may mediate the anorexia and weight loss which is observed in chronic infections and inflammatory conditions. 2. Plasma leptin and soluble tumour necrosis factor receptor (sTNF-r55) concentrations were measured in patients with inflammatory bowel disease and acquired immunodeficiency syndrome (AIDS), and healthy controls. 3. The patients with AIDS were severely wasted [% body fat 12 (9-16); median (interquartile range)] compared with those with inflammatory bowel disease [25.1 (19-31.5)] and control subjects [29.4 (23.6-37.8)]. Leptin concentrations were highly correlated with percentage body fat in controls (r = 0.74, P < 0.001) and patients with IBD (r = 0.73, P < 0.001) but not in the patients with AIDS (r = -0.024). Leptin concentrations were similar in the inflammatory bowel disease [4.8 (2.6-10.1) ng/ml] and control groups [8.0 (3.1-14.1) ng/ml] but were significantly lower (P < 0.05) in patients with AIDS [1.8 (1.5-2.3) ng/ml] after 23 patients were matched for sex and percentage body fat in patients with inflammatory bowel disease [2.4 (1.8-4.1) ng/ml]. Plasma concentrations of sTNF-r55 were higher in both the patients with inflammatory bowel disease [0.19 (0.16-0.23) ng/ml] and those with AIDS [4.8 (2.8-7.3) ng/ml] compared with controls [0.14 (0.09-0.16) ng/ml] but were not correlated with either percentage body fat or plasma leptin concentrations. 4. Hyperleptinaemia does not appear to mediate the anorexia and weight loss associated with inflammatory bowel disease and AIDS. In patients with AIDS with extreme wasting there was no relationship between body fat and leptin and this may be related to the rapid weight loss which occurs in these patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anorexia; Body Composition; Female; Humans; Inflammatory Bowel Diseases; Leptin; Male; Proteins; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Statistics, Nonparametric; Weight Loss

Leptin, a hormone that is secreted by adipose tissue in proportion to fat stores, regulates energy balance and appetite. Recently, tumor necrosis factor and interleukin-1, cytokines that regulate the host response to infection, have been shown to acutely increase leptin levels, raising the possibility that leptin could mediate the anorexia of some infections. We measured leptin levels in patients with the acquired immunodeficiency syndrome and found that leptin levels were not increased relative to body fat in patients who were anorectic, were losing weight, or had a history of weight loss. Furthermore, leptin levels were not increased during secondary infection, suggesting that elevations in leptin do not play a key role in the anorexia of infections associated with acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Humans; Leptin; Male; Middle Aged; Proteins; Weight Loss