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

A 79-year-old woman presented with an unusual form of obesity limited to the lower half of the body from the waistline down but sparing the lower legs and feet. The patient was massive (360 lbs) and symmetrical. The superior half of the body was normal with no morbid obesity or lipoatrophy. These findings do not correspond to any classic form of lipodystrophy. The fat distribution is reminiscent of a pair of knickers and qualifies for the name "pantaloon obesity."
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PMID:A case of pantaloon obesity. 686 15

A patient with Werner's syndrome, partial lipoatrophy and diabetes mellitus presented several of the metabolic alterations found in obesity and maturity-onset diabetes, in spite of a total body-fat mass which was markedly reduced when compared to randomly-selected women. The data show elevated blood sugar and free fatty acids, hyperinsulinemia, elevated glucaon and suppressed growth-hormone levels. Metabolic studies with isolated adipocytes show evidence of increased lipolytic response to catecholamines, diminished binding of insulin and decreased antilipolytic effect of this hormone. A striking feature of this patient's adipose tissue was the contrast between lipoatrophy in the subcutaneous tissue of the extremities and augmented abdominatl subcutaneous adipose tissue. The adipocyte size in this region was very large (1.6 micrograms lipid/cell) and among the largest ever recorded in this laboratory. It is proposed that a 'regional adiposity', particularly in the abdominal area, with enhanced adipocyte size and adipocyte metabolic contributions, may promote the metabolic events and alterations that are more typically observed in the generalized form of obesity.
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PMID:Possible systemic metabolic effects of regional adiposity in a patient with Werner's syndrome. 699 62

Using the molecular scanning technique of single-stranded conformational polymorphism (SSCP), we have examined the exons encoding the insulin receptor gene in 26 patients with syndromes of insulin resistance. We found 27 variant sequences, 4 of which were mutations that altered an amino acid. One patient with the Rabson-Mendenhall syndrome was homozygous for a mutation in the extracellular alpha-subunit (Ser to Leu323), one type A insulin-resistant patient was heterozygous for Pro to Leu1178, and another type A insulin-resistant patient was heterozygous for a mutation in the COOH-terminus of the receptor (Arg to Gln1351). The previously reported, and probably functionally insignificant, variant Val to Met985 was detected in one patient. No missense or nonsense insulin receptor mutations were found in any patients whose insulin resistance was associated with gross obesity, lipoatrophy, or acromegaloid features. No missense or nonsense mutations were found in subjects with polycystic ovary syndrome or Syndrome X. Putting these findings in the context of other work in this field, we conclude that subjects with leprechaunism or Rabson-Mendenhall syndrome have a high probability of having a missense or nonsense insulin receptor mutation. Nonobese, nondysmorphic, severely insulin-resistant females with hirsutism, acanthosis nigricans, and menstrual disturbance (type A phenotype) have an intermediate probability of having this type of insulin receptor mutation. Although insulin receptor mutations have been occasionally described in other phenotypes of insulin resistance, the frequency of point mutations in the exons of the insulin receptor gene in patients with those phenotypes appears to be low.
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PMID:Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. 831 8

We determined the chromosomal localization and partial genomic structure of the coding region of the human PPAR gamma gene (hPPAR gamma), a nuclear receptor important for adipocyte differentiation and function. Sequence analysis and long PCR of human genomic DNA with primers that span putative introns revealed that intron positions and sizes of hPPAR gamma are similar to those previously determined for the mouse PPAR gamma gene[13]. Fluorescent in situ hybridization localized hPPAR gamma to chromosome 3, band 3p25. Radiation hybrid mapping with two independent primer pairs was consistent with hPPAR gamma being within 1.5 Mb of marker D3S1263 on 3p25-p24.2. These sequences of the intron/exon junctions of the 6 coding exons shared by hPPAR gamma 1 and hPPAR gamma 2 will facilitate screening for possible mutations. Furthermore, D3S1263 is a suitable polymorphic marker for linkage analysis to evaluate PPAR gamma's potential contribution to genetic susceptibility to obesity, lipoatrophy, insulin resistance, and diabetes.
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PMID:Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-gamma (hPPAR gamma) gene. 916 28

Patients with insulin resistance and/or type 2 diabetes have a 5-fold increase in cardiovascular mortality rate. Therefore, it is a current issue of discussion that arterial hypertension, lipid disorders as well as visceral obesity are coronary risk factors, which might belong to a syndrome that is caused by decreased insulin sensitivity. Concerning a possible molecular link between insulin resistance, atherosclerosis and obesity, we focus in our research on questions looking for a molecular link between lipid metabolism, insulin action, and obesity at a gene regulatory level. Alterations in the structure, function and regulation of transcription factors appear to be such signalling steps which might play an essential role in the pathogenesis and therapy of cardiovascular risk factors associated with insulin resistance, eg the so called metabolic syndrome. Recent examples are members of the nuclear hormone receptor superfamily, eg peroxisome proliferator-activated receptor (PPAR) isoforms and sterol regulatory element-binding proteins (SREBPs). Beside their regulation by different metabolites, these transcription factors are also targets of hormones, like insulin and leptin, growth factors, and inflammatory signals. Therefore, they appear to be a point of signalling convergence at a gene regulatory level. Major signalling pathways coupling receptors at the cell surface for hormones, growth factors as well as cytokines to gene regulatory events in the nucleus are the MAP-kinase cascades. We have recently defined different postreceptor defects in these pathways in patients with clinical phenotypes corresponding to congenital lipoatrophy. Therefore, these studies may identify novel pathways which play a role in the control of body weight, insulin sensitivity and cardiovascular risk.
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PMID:Insulin-regulated transcription factors: molecular link between insulin resistance and cardiovascular risk factors. 1146 84

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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PMID:The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. 1147 13

Recent advances regarding the biology of adipose tissue have demonstrated that white adipose tissue (WAT) plays a central role in the regulation of energy balance and acts as a secretory/endocrine organ that mediates numerous physiological and pathological processes. Dysregulation of WAT mass causes obesity or lipoatrophy, two disorders associated with life-threatening pathologies, including cardiovascular diseases and diabetes. Alterations in WAT mass result from changes in adipocyte size and/or number. Change in adipocyte number is achieved through a complex interplay between proliferation and differentiation of preadipocytes. Adipocyte differentiation or adipogenesis is a highly controlled process that has been extensively studied for the last 25 years. In vitro preadipocyte culture systems that recapitulate most of the critical aspects of fat cell formation in vivo have allowed a meticulous dissection of the cellular and molecular events involved in the adipogenesis process. The adipogenic transcription factors peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer binding protein-alpha play a key role in the complex transcriptional cascade that occurs during adipogenesis. Hormonal and nutritional signaling affects adipocyte differentiation in a positive or negative manner, and components involved in cell-cell or cell-matrix interactions are also pivotal in regulating the differentiation process. This knowledge provides a basis for understanding the physiological and pathophysiological mechanisms that underlie adipose tissue formation and for the development of novel and sound therapeutic approaches to treat obesity and its related diseases.
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PMID:Adipocyte differentiation: from fibroblast to endocrine cell. 1174 35

Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation-stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin-induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation-stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation-stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation-stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin-resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator-activated receptor-gamma; an action may contribute to the insulin-sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.
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PMID:Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. 1179 Sep 63

Obesity and lipoatrophy are major risks for insulin resistance, type 2 diabetes and cardiovascular diseases. The molecular links between adipocyte dysfunction and metabolic disorders were elusive until the discovery that adipose tissue operates as an endocrine organ and releases factors targeting a wide range of organs. This article attempts to review the more recent advances from research on the transcriptional control of adipogenesis and on new adipocyte-secreted proteins that have been proposed as molecular links between adipose tissue and insulin resistance.
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PMID:New factors in the regulation of adipose differentiation and metabolism. 1204 92

Obesity is commonly associated with the development of insulin resistance and diabetes in humans and rodents. Insulin resistance and diabetes are observed in lipoatrophic individuals or rodent models of lipoatrophy. Here we focus on the role of leptin, the product of the obesity (ob) gene, in the development of insulin resistance and diabetes associated with obesity and lipoatrophy. We review the reported effects of leptin on whole body glucose metabolism and compare and contrast these with direct effects on skeletal muscle, fat and liver. This summary of paradoxical observations on the effects of leptin on glucose homeostasis and the ability of leptin to induce or improve insulin resistance suggests that a complex interplay exists between direct peripheral and centrally mediated effects of the hormone. Evidence suggesting that leptin acts as a mediator of insulin release from pancreatic beta cells is reviewed. Finally, intracellular signaling mechanisms stimulated by both leptin and insulin are discussed, with potential points of cross-talk suggested.
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PMID:Analysis of paradoxical observations on the association between leptin and insulin resistance. 1215 84


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