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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, our understanding of adipose tissue physiology and function has undergone an enormous transformation. Once considered a passive storage receptacle with a fixed number of cells and limited purpose, adipose tissue is now recognized as a complicated organ with important endocrine and metabolic functions. It is now known that both increased and decreased adipose tissue mass, as seen in obesity, anorexia, and lipodystrophy, have profound effects on multiple body systems, including immune, reproductive, and hematopoietic. The study of adipose tissue, therefore, is important not only for those who treat obesity, lipoatrophy, and their associated metabolic and endocrine derangements, but also for those dermatologists who specialize in the medical and surgical treatment of disorders within the body's largest adipose tissue subdivision, the subcutaneous fat. This introductory article is the first in a series about adipose tissue in normal and diseased states.
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PMID:Subcutaneous fat in normal and diseased states: 1. Introduction. 1619 90

Obesity and lipoatrophy are major risks for insulin resistance, non-insulin-dependent diabetes and cardiovascular disease. In the past three decades, significant advances have been made in delineating the key transcription factors of adipogenesis, as well as extracellular effectors and intracellular signalling pathways that regulate fat cell formation. This review focuses on in vitro models of adipocyte differentiation, and on the balance between pro- and anti-adipogenic factors that drive the adipocyte differentiation process. Full understanding of the mechanisms of adipose tissue differentiation represents a major issue to develop a comprehensive strategy to prevent and treat obesity.
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PMID:Adipogenesis: cellular and molecular aspects. 1631 Dec 13

Obese individuals often suffer from negative self-image. Many, even those with a normal body mass index, resort to pharmacotherapy (lipase inhibitors or appetite suppressants), mesotherapy and surgery (gastric volume reduction, liposuction or apronectomy) in a bid to remove excess adipose tissue. These treatments are associated with inherent morbidity and even mortality, and hence should not be undertaken lightly. The observation that denervation of adipose tissue results in lipoatrophy leads us to postulate that chemodenervation using botulinum toxin may achieve the same result, i.e. fat loss, and we explore the methods by which selective fat loss may be achieved. We concede that removal of subcutaneous fat does not, however, reduce the risks associated with the metabolic syndrome, as visceral (intra-abdominal) fat is not reduced by the removal of subcutaneous fat.
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PMID:Botulinum toxin injections to reduce adiposity: possibility, or fat chance? 1671 33

Dyslipidemia and insulin resistance occur in a large proportion of HIV-infected patients treated with highly active antiretroviral therapy (HAART); anthropomorphic changes, such as lipoatrophy and central obesity, occur in a subset of patients. This cluster of clinical features, which is termed HIV lipodystrophy, places patients at increased risk for cardiovascular disease. Currently, there is no consensus on the appropriate therapy for the management of HIV lipodystrophy for which the underlying defects are enhanced lipolysis, impaired fat oxidation, increased hepatic VLDL-triglyceride synthesis and secretion, and impaired disposal of intestinally-derived lipoprotein-triglycerides. We describe the design of a randomized, placebo-controlled trial to compare the effects of usual care to diet, exercise and lipid-lowering drugs on lipid profiles of patients with HIV lipodystrophy. The trial will randomize 200 patients into five groups. Outcomes of usual care, diet and exercise alone or in combination with niacin, fenofibrate or both medications will be compared after six months. Unique aspects of the design include an interactive Internet Diet Management system to increase ATP-III recommended dietary compliance for metabolic syndrome, and a supervised program of aerobic and resistance exercises. The study is powered to detect a 20% decrease in triglycerides with the lifestyle intervention and an additional 20% improvement with the addition of niacin and/or fenofibrate. Secondary outcomes include assessment of lipid profile changes, LDL and HDL particle size, plasma cholesterol ester transport protein activity, visceral and subcutaneous fat distribution, glucose tolerance, insulin resistance, and leptin and adiponectin levels.
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PMID:Heart positive: design of a randomized controlled clinical trial of intensive lifestyle intervention, niacin and fenofibrate for HIV lipodystrophy/dyslipidemia. 1691 90

Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.
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PMID:Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications. 1693 9

White adipose tissue (WAT) is now recognized as a highly active metabolic tissue and important endocrine organ producing numerous peptides and proteins with broad biological activity. The term adipokines has been coined to refer to a series of adipocyte-derived biologically active molecules, which may influence the function as well as the structural integrity of other tissues. Adipokines are implicated in control of food intake, energy balance and body weight (leptin), glucose homeostasis (e.g., adiponectin, resistin, adiponutrin), lipid metabolism (e.g., retinol-binding protein, cholesterolester transfer protein), angiogenesis (vascular endothelial growth factor VEGF), fibrinolytic system (plasminogen activator inhibitor-1 PAI-1), pro- and anti-inflammatory effects (e.g., tumor necrosis factor-alpha TNF-alpha, interleukin-6 IL-6) or sexual development and reproduction (leptin). Alterations of WAT mass in obesity or lipoatrophy effect the production of most adipose secreted factors. Besides others, alcohol consumption affects also hormonal system leading to non-physiological increase/decrease of hormone gene expression and plasma hormone concentrations appearing as final poor or stronger effects on target tissues. As mentioned above, white adipose tissue is important endocrine organ, so alcohol intake can alter also adipokines expression in WAT and adipokines plasma levels and in this way it can affect the adipokine-targeted tissues and their functions.
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PMID:Alcohol intake modulates hormonal activity of adipose tissue. 1710 May 51

Lipodystrophy is a common alteration in HIV 1-infected patients under anti-retroviral treatment. This syndrome is usually associated with peripheral lipoatrophy, central adiposity and, in some cases, lipomatosis, as well as systemic insulin resistance and hyperlipidemia. Research on the ethiopathogenesis of the disease revealed novel aspects of adipose tissue biology highly relevant to obesity research: the pivotal role of mitochondria in white adipose tissue function, the role that interference with master transcription factors of adipogenesis may have in human adipose tissue, the capacity of human white adipose tissue to acquire brown fat-like features, as well as the importance of apoptosis and the potential impact of viral infections in adipose tissue. The dramatic difference between subcutaneous adipose depots, prone to lipoatrophy, and the visceral adipose depots, prone to enlargement, has been further evidenced in the study of the lipodystrophy syndrome. The recognition of a local pro-inflammatory environment in lipoatrophic adipose tissue from affected patients, including macrophage infiltration and enhanced expression of chemokines and cytokines, points to events paradoxically similar to those in the hypertrophied adipose tissue in obesity. However, this also potentially provides an explanation for the existence of systemic alterations common to lipodystrophy and obese patients and reminiscent of the metabolic syndrome.
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PMID:Lipodystrophy in HIV 1-infected patients: lessons for obesity research. 1765 62

The use of highly active antiretroviral therapy (HAART) in HIV-1 infection confers immunological and survival advantages, at the cost of induction of significant metabolic disturbances. These include insulin resistance, disturbances in lipid metabolism, glucose homeostasis, adipocyte physiology and body fat partitioning with peripheral lipoatrophy and visceral obesity. These metabolic disturbances produce clinical manifestations which impact on the future health of the HIV-infected patient, including hyperlipidaemia, lipodystrophy, metabolic syndrome, cardiovascular disease and type 2 diabetes. These conditions are evident in the relative short term as HAART (and possibly HIV infection) appears to accelerate their pathogenesis. The current understanding of the mechanisms and time courses for developing metabolic complications on HAART is reviewed in this paper. The efficacy of therapeutic interventions for insulin resistance, hyperlipidaemia, body fat partitioning disorders and metabolic syndrome is summarized.
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PMID:Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection. 1807 Aug 30

Treated HIV infection and HIV-lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection.
Obesity (Silver Spring) 2009 Jan
PMID:Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection. 1900 69

Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.
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PMID:Leptin in humans: lessons from translational research. 1917 40


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