Endocrine Function Of Adipose Tissue Research Articles

Serum Adiponectin and Leptin Concentrations in HIV-Infected Children with Fat Redistribution Syndrome

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.

Mechanisms of Disease: hepatic steatosis in type 2 diabetes—pathogenesis and clinical relevance

Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.

The endocrine function of adipose tissue: an update

Adipose tissue secretes bioactive peptides, termed 'adipokines', which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity-related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF-alpha and IL-6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients.

Metabolic Actions of Adipocyte Hormones: Focus on Adiponectin

The obesity epidemic has focused attention on the endocrine function of adipose tissue. Adipose tissue secretes leptin, cytokines, complement factors, and components of the coagulation cascade, most of which are increased in obesity. In contrast, a strong negative correlation exists between adiponectin and adiposity, insulin sensitivity, diabetes, vascular inflammation, and atherosclerosis. Adiponectin treatment in rodents increases insulin sensitivity and reduces lipids and atherogenesis. Chronic and central adiponectin treatment reduces weight, glucose, and lipids. The insulin-sensitizing action of thiazolidinediones is mediated, in part, through adiponectin. A causal role of adiponectin in diabetes, dyslipidemia, and atherosclerosis has been established in knockout mice. Therefore, adiponectin seems to be a marker of obesity-related diseases and a potential therapeutic target.

The Endocrine Function of Adipose Tissue

The traditional view of the adipocyte as a passive receptacle for storage and combustion of triacylglycerol is undergoing rapid change. It is now recognized that a variety of adipocyte and adipose stromal cell derived bioactive peptides, collectively termed “adipokines”, act both locally and distally through autocrine, paracrine and endocrine effects. Alteration of adipose tissue mass in obesity increases the production of most adipose secreted factors; therefore white adipose tissue could play a key role in multiple metabolic disorders and in the increased risk of cardiovascular disease associated with obesity. In fact, increased activity of tumor necrosis factor and interleukin 6 are involved in the development of the insulin resistance present in obesity. In contrast, other adipokines, like adiponectin and leptin, are insulin sparing through stimulatory affects on the beta oxidation of fatty acids in skeletal muscle. Other adipokine have been implicated in hypertension (angiotensinogen) and impaired fibrinolysis (PAI-1). The role of resistin is poorly understood: this protein seems surely implicated in insulin resistance in rats, but probably not in humans. Reduction of adipose tissue mass, through weight reduction in association with exercise, has been shown to improve the adipokines production (reduction in TNF-α and IL-6, increase in adiponectin) while the thiazolinedione drugs increase endogenous adiponectin production. These results support the idea that the development of new drug targeting adipokines might represent a promising therapeutic approach to protect obese patients from atherosclerosis. This paper will review the function and the regulation of adipocytokines in order to understand how obesity may contribute to metabolic syndrome.

Effect of DHEA on endocrine functions of adipose tissue, the involvement of PPARγ

Dehydroepiandrosterone (DHEA), an adrenal steroid, is known to decrease body fat. Thus, it may also alter the endocrine functions of adipose tissue. The aim of this study was to determine if administration of DHEA might influence adiponectin gene expression and secretion from adipose tissue. We demonstrate here the inducing effect of exogenously administered DHEA on adiponectin gene expression in epididymal WAT and adiponectin levels in serum of rats fed a DHEA-containing diet (0.6%, w/w) for 2 weeks, accompanied by a reduction in epididymal adipose tissue mass. A corresponding increase in peroxisome proliferator-activated receptor γ (PPARγ) mRNA expression suggests that PPARγ may be involved in the up-regulation of adiponectin gene expression after DHEA treatment. The presented observations indicate that the positive effects of DHEA, which seems to play a protective role against insulin resistance and atherosclerosis, may be in fact indirect and due to up-regulation of adiponectin gene expression and stimulation of adiponectin secretion from adipose tissue.

Decreased Plasma Adiponectin Concentrations Are Closely Related to Steatosis in Hepatitis C Virus-Infected Patients

The mechanisms underlying steatosis during hepatitis C virus (HCV) infection are complex and multifactorial. Obesity is a well-recognized risk factor for the development of steatosis in chronic hepatitis C infection. The aim of our study was to investigate the role of adipocytokines in HCV-related steatosis. Therefore, we hypothesized that the endocrine function of adipose tissue could be, in part, responsible for HCV-related steatosis. Seventy-one consecutive untreated chronic hepatitis C patients were studied to assess the effects of adipocytokines, body mass index (BMI), age, and HCV genotype on steatosis. We used ELISA to determine serum adiponectin, leptin, and soluble TNF receptors I and II concentrations. Steatosis was observed in 42 (59.1%) patients. BMI was significantly associated with leptin (r = 0.64; P = 0.0001) and was border significantly associated with adiponectin concentrations (r = -0.22; P = 0.06). In univariate analyses, age, HCV genotype 3, BMI, increased leptin level, increased insulin level, and decreased adiponectin concentration were associated with steatosis. In multivariate analysis, steatosis was significantly associated with low adiponectin concentration, age, HCV genotype 3, and aspartate aminotransferase (ASAT) level, whereas steatosis was not associated with leptin, insulin, and BMI. In chronic HCV patients, hypoadiponectinemia is significantly associated with the development of liver steatosis. The fact that the plasma levels of adiponectin inversely correlate with steatosis in HCV-infected subjects suggests that hypoadiponectinemia may contribute to hepatic steatosis progression and liver injury in this population. One practical implication is that therapy to increase circulating adiponectin concentration, such as overweight reduction or thiazolidinediones, provides the potential to improve steatosis in chronic hepatitis C infection.

Ageing and plasma adiponectin concentration in apparently healthy males and females

It is well known that ageing is associated with several hormonal alterations. However, the consequence of ageing on the endocrine function of adipose tissue is not fully elucidated. Adiponectin is a new anti-inflammatory protein secreted exclusively by adipocytes and plays a protective role against insulin resistance and atherosclerosis. Therefore, the aim of present study was to estimate plasma adiponectin concentration in apparently healthy elderly subjects. Fifty-eight women and 67 men aged 20-93 years were included in this study. Subjects were divided into three groups: younger than 50 years, between 50 and 70 years and older than 70 years of age. Plasma adiponectin concentration was estimated by an enzyme-linked immunosorbant assay in blood samples withdrawn in the morning after overnight fasting. In males plasma testosterone and dehydroepiandrostendione sulphate concentrations were assessed by a radioimmunoassay method. Plasma adiponectin concentration only tended to be higher in all elderly subjects (above 70 years) than in the group of all subjects aged between 50 and 70 and the group younger than 50 years of age (12.8 +/- 5.7; 9.9 +/- 5.7 and 10.7 +/- 5.4 microg/ml, respectively). Plasma adiponectin concentration was of similar magnitude in female subjects of these three groups (11.2 +/- 5.7; 11.2 +/- 6.8 and 11.7 +/- 4.9 microg/ml, respectively). In contrast, males over 70 years old are characterized by significantly higher plasma adiponectin (14.0 +/- 5.4 microg/ml) concentration than males between 50 and 70 years of age (8.9 +/- 4.7 microg/ml, P < 0.01) and males younger than 50 years of age (9.6 +/- 5.7 microg/ml, P < 0.05). In the entire studied group a significant but weak, positive correlation was found between plasma adiponectin concentration and age (tau = 0.12; P = 0.04). Additionally, significant correlation was found between plasma adiponectin concentration and age in males when analysed separately (tau = 0.28; P = 0.0007). Such correlation was not significant in females (tau = -0.06; P = 0.5). Plasma adiponectin concentration in females did not change significantly with age. In contrast to females, elderly males over 70 years of age are characterized by significantly higher plasma adiponectin concentration than younger ones.

Adipose tissue as an endocrine organ.

Adipose tissue is a complex, essential, and highly active metabolic and endocrine organ. Besides adipocytes, adipose tissue contains connective tissue matrix, nerve tissue, stromovascular cells, and immune cells. Together these components function as an integrated unit. Adipose tissue not only responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine functions. These factors include leptin, other cytokines, adiponectin, complement components, plasminogen activator inhibitor-1, proteins of the renin-angiotensin system, and resistin. Adipose tissue is also a major site for metabolism of sex steroids and glucocorticoids. The important endocrine function of adipose tissue is emphasized by the adverse metabolic consequences of both adipose tissue excess and deficiency. A better understanding of the endocrine function of adipose tissue will likely lead to more rational therapy for these increasingly prevalent disorders. This review presents an overview of the endocrine functions of adipose tissue.

Adiponectin is reduced in gestational diabetes mellitus in normal weight women.

Adiponectin is an adipose tissue-derived protein counteracting insulin resistance and inflammation. We have compared women with gestational diabetes mellitus (GDM; n = 22) and normal pregnancies (controls; n = 29) to evaluate whether adiponectin represents a link between endocrine function of adipose tissue and the development of diabetes during pregnancy. The participants were categorized according to their prepregnancy body mass index (BMI) into two classes: BMI < 25 and BMI = 25. Plasma concentrations of adiponectin, leptin and insulin were measured by radioimmunoassay (RIA). Total cholesterol, high density lipoprotein (HDL) cholesterol and triacylglycerol were determined by routine enzymatic methods. Expression of adiponectin/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was determined by real-time reverse transcription polymerase chain reaction (RT-PCR) in subcutaneous adipose tissues obtained by excision at cesarean delivery. Among individuals with GDM and BMI < 25 kg/m2 (n = 8), plasma adiponectin concentration was lower than in the controls (n = 20), 8.1 +/- 1.2 microg/mL vs. 12.2 +/- 1.1 microg/mL; p = 0.04). The mean plasma leptin concentrations did not differ between the GDM and control groups. Plasma concentrations of insulin and C-peptide were significantly higher among GDM than control individuals independent of BMI. For all the women included in the study, we found that plasma adiponectin only correlated negatively with prepregnancy and third-trimester (sampling day) BMI (p = 0.03 vs. p = 0.01). In abdominal subcutaneous adipose tissue of pregnant women, adiponectin mRNA levels were lower in GDM than in control subjects (0.77 +/- 0.18 vs. 1.39 +/- 0.15; p = 0.05). These results indicate that low plasma adiponectin concentration is associated with GDM. In addition, we found that adiponectin mRNA levels in adipose tissue biopsies from GDM subjects were reduced.

Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases.

Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity.

Adipose tissue as an endocrine organ.

Adipose tissue is a highly active endocrine organ secreting a range of soluble products with both local and distant actions. These hormones have important roles in metabolism, reproduction, cardiovascular function and immunity. It is now evident that adipose endocrine function directly influences other organ systems, including the brain, liver and skeletal muscle. The endocrine function of adipose tissue is significantly regulated by nutritional status, and both are inextricably linked to the energy storage role of adipose tissue. This chapter highlights the endocrinology of adipose tissue by concentrating on functional aspects of the secreted products. The data of particular relevance to humans are highlighted, and areas in need of future research are suggested.

Adipoendocrinology and adipoparacrinology: emerging fields of study on the adipose tissue

Adipose tissue was conceived originally as merely passive, space-filling, fat storage tissue. However, in the last 10 years, investigations aimed at studying the endocrine secretion by adipose tissue have enjoyed explosive growth. The major secretory compartment of adipose tissue consists of adipocytes and stromal fibroblasts (adipofibroblasts). These cells secrete multiple bioactive molecules, conceptualized as adipokines or adipocytokines. Overall, this intellectual grown process framed an emerging field of study, adipoendocrinology. Adipoendocrinology connotes the study of the cellular and molecular biology of the endocrine function of adipose tissue in normal and diseased conditions. In humans, white adipose tissue is partitioned into a few large depots, including visceral and subcutaneous location, and many small depots, associated with heart, large blood vessels, major lymph nodes and other organs. The possibility that the endocrine secretory activity of large adipose depots may directly contribute to the elevated plasma levels of disease-associated adipokines has recently gained considerable attention. However, the paracrine secretory activity of organ-associated adipose tissue (the small adipose depots) has until now attracted little attention in the adipobiology of disease. Here we attempt to emphasize that studies aimed at evaluation of the paracrine secretion of organ-associated adipose tissue are becoming mandatory, since identification of the secreted molecules, particularly, adipokines, may yield clues to a possible transmission of pathogenic and/or protective stimuli, from the associated adipose tissue towards the interior of the associating organ. In this review we summarize most of the current information about adipoendocrinology and adipoparacrinology of various diseases. Biomedical Reviews 2001; 12: 31-39.

Endocrine functions of adipose tissue: view from the chair.

Endocrine functions of adipose tissue: view from the chair.