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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is the first of a group of adipocyte-secreted hormones to be used clinically to treat hypoleptinemic states. In children with congenital leptin deficiency and extreme obesity, leptin induces satiety and a dramatic loss of weight. In hypoleptinemic patients with extreme insulin resistance and lipodystrophy, leptin ameliorates insulin resistance, hyperglycemia, hyperinsulinemia, dyslipidemia and hepatic steatosis. In both these leptin-deficient states, leptin therapy restores gonadotrophin secretion, as well as luteinizing hormone and thyroid-stimulating hormone pulsitility.
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PMID:The clinical uses of leptin. 1464 19

GH and PRL are both implicated in adipose tissue development. Whilst direct effects of GH have been clearly demonstrated, direct effects of PRL have been subject to considerable debate. Recent studies have however provided compelling evidence for PRL receptors on adipocytes and in vitro effects on leptin and lipoprotein lipase activity have been demonstrated. Quantitatively however these effects of PRL are less significant than those of GH and the most pronounced effects of PRL on adipose tissue are indirect, for example, during lactation, when prolactin drives milk synthesis which results in a homeorhetic shift towards lipid mobilization from adipose tissue to support milk production. GH also exhibits such homeorhetic effects, most notably in ruminants, but also clearly has direct, insulin-antagonistic, metabolic effects. The roles of GH and PRL on adipocyte proliferation and differentiation have also been controversial, with GH stimulating adipocyte differentiation in vitro in cell lines whilst stimulating proliferation and inhibiting differentiation of primary cell cultures. Examination of adipose tissue development in PRLRko and GHRko mice has revealed roles for both hormones. PRLRko mice show impaired development of both internal and subcutaneous adipose tissue due to decreased numbers of adipocytes. In contrast, GHRko mice exhibit major decreases in the number of internal (parametrial) adipocytes whereas subcutaneous adipocytes develop almost normally. This leads to major changes in the sites of adipose tissue accretion and bears interesting parallels with the adipose tissue redistribution which occurs in HIV-induced lipodystrophy. Such individuals exhibit a central obesity which can be partially corrected by GH treatment. However, recent studies suggest that this may be a physiological response in which adipose tissue sites containing lymphoid tissue (such as mesenteric) show preservation of adipose tissue perhaps to support augmented immune responses.
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PMID:Effects of growth hormone and prolactin on adipose tissue development and function. 1470 19

The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose metabolism in vivo during hyperinsulinemic-euglycemic clamps in awake mice. Pretreatment of IL-6 blunted insulin's ability to suppress hepatic glucose production and insulin-stimulated insulin receptor substrate (IRS)-2-associated phosphatidylinositol (PI) 3-kinase activity in liver. Acute IL-6 treatment also reduced insulin-stimulated glucose uptake in skeletal muscle, and this was associated with defects in insulin-stimulated IRS-1-associated PI 3-kinase activity and increases in fatty acyl-CoA levels in skeletal muscle. In contrast, we found that co-treatment of IL-10, a predominantly anti-inflammatory cytokine, prevented IL-6-induced defects in hepatic insulin action and signaling activity. Additionally, IL-10 co-treatment protected skeletal muscle from IL-6 and lipid-induced defects in insulin action and signaling activity, and these effects were associated with decreases in intramuscular fatty acyl-CoA levels. This is the first study to demonstrate that inflammatory cytokines IL-6 and IL-10 alter hepatic and skeletal muscle insulin action in vivo, and the mechanism may involve cytokine-induced alteration in intracellular fat contents. These findings implicate an important role of inflammatory cytokines in the pathogenesis of insulin resistance.
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PMID:Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. 1504 22

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor alpha, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.
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PMID:Diabetes, lipids, and adipocyte secretagogues. 1505 36

We recently identified mutations in the lipin gene, Lpin1, as the cause of lipodystrophy in the fatty liver dystrophy (fld) mouse. Here we identify impaired adipocyte differentiation as the basis for lipodystrophy in lipin-deficient mice and demonstrate that lipin is required for normal induction of the adipogenic gene transcription program. We found that the reduced adiposity in chow fed fld mice and resistance to obesity in fld mice fed a high-fat diet is associated with reduced adipogenic gene expression. Using primary mouse embryonic fibroblasts isolated from fld mice, we confirmed that lipin deficiency prevents normal lipid accumulation and induction of key adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT enhancer-binding protein (C/EBP)alpha. However, our previous studies of daily gene expression in differentiating 3T3-L1 preadipocytes indicated that lipin expression is undetectable until about day 3 of differentiation, at a point after PPARgamma and C/EBPalpha gene expression is established. This paradox was resolved by examining gene expression at 10-h intervals during 3T3-L1 cell differentiation, leading to detection of transient lipin expression at 10 h into the differentiation program, prior to the induction of PPARgamma and C/EBPalpha. Consistent with a requirement for lipin expression upstream of PPARgamma, differentiation of lipin-deficient mouse embryonic fibroblasts could be rescued by ectopic expression of PPARgamma. Thus, we conclude that lipin expression is required prior to PPARgamma during adipocyte differentiation.
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PMID:Lipin expression preceding peroxisome proliferator-activated receptor-gamma is critical for adipogenesis in vivo and in vitro. 1512 8

The metabolic syndrome (MetS) is a common multiplex cluster of phenotypes strongly related to cardiovascular disease that includes central obesity with hypertension, dyslipidemia, and type 2 diabetes. The core molecular defect of the MetS is insulin resistance; indeed, the terms "MetS" and "insulin resistance syndrome" often are used interchangeably. The successful translation to clinical medicine of molecular genetic research on other rare monogenic metabolic disorders has stimulated the evaluation of such rare monogenic forms of insulin resistance as partial lipodystrophy resulting from mutations in either LMNA or PPARG genes. Careful phenotypic evaluation of carriers of monogenic insulin resistance using a range of diagnostic methods--an approach sometimes called "phenomics"--may help to find early presymptomatic biomarkers of cardiovascular disease, which, in turn, may uncover new pathways and targets for interventions for the common MetS, diabetes, and atherosclerosis.
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PMID:Phenomics, lipodystrophy, and the metabolic syndrome. 1517 63

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) is a novel adipocytokine with important metabolic effects. It is physiologically released from adipose tissue and circulates in serum as a hexamer and larger multimeric structure of high molecular weight. Serum level of the protein correlates with systemic insulin sensitivity. Recently adiponectin receptors AdipoR1 and AdipoR2 have been discovered by expression cloning. AdipoR1 is abundantly expressed in skeletal muscles, whereas AdipoR2 is predominantly expressed in the liver. Marked expression of mRNA for AdipoR1 and AdipoR2 has been lately reported in pancreatic beta cells. Both of the receptors activate AMPK and PPAR alpha metabolic pathways leading to an increase in fatty acid oxidation, glucose uptake and a decreased rate of gluconeogenesis, thus enhancing insulin sensitivity. Moreover effects of adiponectin mimic many metabolic actions of insulin such as augmenting blood flow and glucose disposal in NO-dependent manner. The precise mechanism of regulation of plasma adiponectin level is unknown. Recently the mechanism of transcriptional activation of adiponectin gene via PPAR gamma was described. Its level seems to be decreased by TNFalfa and beta-adrenergic agonists. Furthermore there is increasing evidence that some genetic variants in the adiponectin gene may be associated with its ethnical differences in level as well as its likely clinical consequences. Hipoadiponectynemia is associated with obesity, metabolic syndrome, diabetes type 2, cardiovascular disease, lipodystrophy in AIDS. In patients with chronic renal failure, anorexia nervosa plasma adlponectin level is increased. Weight loss and therapy with thlazolidinediones are proved to enhance endogenous adlponectin production in humans. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and antiatherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, especially in individuals with low plasma levels of adiponectin.
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PMID:[Adiponectin--adipocytokine with a broad clinical spectrum]. 1523 Jan 53

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor with a key role in adipocyte differentiation. Since 1997, studies of rare mutations and common polymorphisms of the PPARgamma gene have enabled us to expand our knowledge of the role of this transcription factor in humans. Rare monogenic mutations in PPARgamma have a limited impact on the health of the population due to their low frequency but are associated with severe phenotypes such as severe insulin resistance, partial lipodystrophy, type 2 diabetes and hypertension. Conversely, common polymorphisms of PPARgamma with a relatively high frequency can have a significant impact on the general population. Although they may modulate the risk of developing type 2 diabetes, obesity and cardiovascular diseases, the data remains controversial. This review details and discusses results obtained for PPARgamma variants, whose effects sometimes appear discordant.
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PMID:Impact of genetic variation of PPARgamma in humans. 1546 24

Nutritional status has a prognostic value in the clinical evolution of patients who are malnourished, are becoming malnourished or are in process of being rehabilitated. The evaluation of nutritional status is based on a comprehensive approach, and includes body composition measurement by bio-impedance analysis (BIA). BIA determines the quantity of body fat-free and fat mass and has a precision around 4%. The reliability of BIA depends on the use of body composition prediction equations that are adapted to the subjects studied and on the inclusion of various anthropometric parameters (weight, height, sex, age, race, etc). BIA remains imprecise in the presence of abnormal distribution of body compartments (ascites, dialysis, lipodystrophy) or of extreme weights (cachexia, severe obesity). Multi-frequency or segmental BIA were developed to overcome hydration abnormalities and variations in body geometry. However, these techniques require further validation. This review discusses the indications and limitations of BIA.
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PMID:[Role of impedance measurement in nutritional screening]. 1557 4

Humans respond to an acute excess of ingested energy by storing the surplus energy as triglyceride in white adipose tissue. To study the energetic response to acute overfeeding in human subjects with limited adipose tissue capacity, we recruited seven subjects with lipodystrophy and seven lean healthy controls. Total fat mass was approximately 70% lower in lipodystrophic subjects (mean, 6.1 kg) than in body mass index-matched lean controls (mean, 22.0 kg). Energy expenditure and macronutrient oxidation rates were assessed in chamber calorimeters on two separate occasions for 40 h, during which time subjects consumed either an energy-balanced diet or a diet incorporating 30% excess energy as fat. On the energy-balanced diet, total daily energy expenditure and basal metabolic rate were linearly associated with lean mass in both groups (r(2) = 0.83) and were not significantly different between groups when corrected for lean mass. In response to the fat challenge, total energy expenditure did not increase significantly in healthy controls (9,472 +/- 1,069 to 9,724 +/- 1,114 kJ/d; P = 0.189). Substrate oxidation results confirm that excess fat was predominantly stored. In contrast, lipodystrophic subjects significantly increased total daily energy expenditure (11,081 +/- 1,226 to 11,730 +/- 1,374 kJ/d; P < 0.005). This was largely attributable to a 29% increase in fat oxidation. Thus, subjects with lipodystrophy uniquely respond to an acute hypercaloric load with a higher energy expenditure increment and by increasing fat oxidation. Insight into the molecular mechanisms responsible for this phenomenon may yield novel therapeutic approaches for obesity.
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PMID:Energy expenditure and adaptive responses to an acute hypercaloric fat load in humans with lipodystrophy. 1561 17


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