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

Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.
Mol Cell Endocrinol 1977 Oct
PMID:Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes. 20 May 11

1. Variables involved in the genesis of hypertension in male broad-breasted white turkeys include social environment, obesity and high salt intake. 2. The hypertension is characterized by low plasma renin activity and, with increasing age, normal to high plasma aldosterone. 3. Medionecrosis of the abdominal aorta is a common pathological finding. 4. The absence of atherosclerotic plaques is probably related to the high concentrations of alpha-lipoproteins.
Clin Sci Mol Med Suppl 1978 Dec
PMID:The natural history of hypertension in turkeys. 28 53

1. The esterification of exogenous palmitate to diglyceride and triglyceride in adipocytes was studied in obese and diabetic patients with and without hypertriglyceridaemia. The rate of esterification correlated significantly with the triglyceride content of adipocytes. 2. In diabetic patients with hypertriglyceridaemia, the rate of esterification to triglyceride was significantly greater than in diabetic patients with normotriglyceridaemia. This difference could not be attributed to differences in glucose tolerance or to the degree of obesity. 3. Fasting plasma insulin levels were greater in the hypertriglyceridaemic group than in the normotriglyceridaemic group. The difference in esterification rates could have been due to differences in adipocyte size. 4. The esterification of fatty acid in adipose tissue of diabetic patients was lower than in non-diabetic subjects and this difference could not be accounted for by differences in adipocyte size or differences in the intracellular pools of fatty acid in adipose tissue. 5. The role of esterification of exogenous fatty acids in adipose tissue as a possible determinant of the uptake of glyceride fatty acids from plasma is discussed.
Clin Sci Mol Med 1976 Sep
PMID:The esterification of exogenous fatty acids by adipose tissue of hypertriglyceridaemic subjects with or without diabetes mellitus. 96 55

beta 3-Adrenergic receptors (beta 3AR) mediate lipolytic and thermogenic responses in rodent adipose tissues in vitro, and "atypical" beta AR agonists that active these receptors have potent therapeutic effects in in vivo rodent models of adult-onset diabetes and obesity. However, experiments with rodent cells that natively express the beta 3AR, as well as those with cells that express cloned rodent beta 3AR, have suggested that the pharmacological properties of the rodent and human beta 3AR differ. Given that rodent models of obesity and diabetes are used to develop human therapeutic agents, we sought to compare directly the ligand-binding and functional properties of the rat and human beta 3AR in parallel studies using Chinese hamster ovary cells expressing the recombinant receptors. The endogenous catecholamines epinephrine (EPI) and norepinephrine (NE) were found to have low affinities (micromolar) for the beta 3AR of both species. The rank orders of potency of various agonists in stimulating adenylyl cyclase were clearly different, i.e., for the human beta 3AR, CGP12177 (CGP) > isoproterenol (ISO) > or = BRL34377 (BRL) = Pindolol > NE > EPI; for the rat, CGP > or = BRL > ISO > or = NE > Pindolol > EPI. The intrinsic activities of various agonists were also different, with the following rank orders (compared with ISO): for the human beta 3AR, NE > EPI > BRL = CGP > Pindolol; for the rat beta 3AR, BRL > NE > EPI > CGP > Pindolol. Competition binding studies with 125I-cyanopindolol and these agonists gave similar rank orders of potency. Thus, although the human and rat receptors exhibited similar properties with respect to catecholamine agonists, numerous differences in the potency and efficacy of synthetic noncatecholamine agonists were noted, indicating that the action of atypical agonists at rodent beta 3AR may not be predictive of therapeutic potential in humans.
Mol Pharmacol 1992 Oct
PMID:Functional properties of the rat and human beta 3-adrenergic receptors: differential agonist activation of recombinant receptors in Chinese hamster ovary cells. 133 54

Obesity is likely to be a multifactorial disease with an important genetic component. Animal models of genetic and experimentally induced obesity suggest that glucocorticoid receptor (GR) activity plays a role in the aetiology and maintenance of the obese state. Glucocorticoid activity appears to be essential for the development of hyperinsulinaemia and subsequent fat deposition. In humans, glucocorticoid excess is associated with central fat distribution. We have therefore investigated the restriction fragment length polymorphisms of the human GR gene locus (GRL) and have sought associations of specific alleles with anthropometric measurements and indices of insulin secretion and resistance in obesity. Fifty-six extremely obese, unrelated, nondiabetic premenopausal British Caucasian females and 43 age-matched, normal weight controls were studied. The obese subjects were characterized by fat distribution (waist to hip ratio), insulin secretion and insulin resistance (fasting insulin (FI)), an index of insulin resistance (HOMA), stimulated insulin secretion during an oral glucose tolerance test and insulin-mediated glucose disposal, steady-state plasma glucose). A Bc1I polymorphism (fragments of 4.5 and 2.3 kb) demonstrated significant association with indices of glucose metabolism in obesity; those subjects homozygous for the 4.5 kb fragment had elevated FI (Pc = 0.012) and HOMA (Pc = 0.012) values. The genotypic and allelic frequencies of the GRL Bc1I polymorphism were otherwise similar in obese and normal weight subjects. We postulate that the GRL Bc1I polymorphism may directly affect GR gene expression, or be in linkage disequilibrium with a possible mutation within one of three exons of the GR gene, and thereby modulate GR transcriptional activity on target genes involved in glucose and insulin homeostasis.
J Mol Endocrinol 1992 Dec
PMID:An association between a Bc1I restriction fragment length polymorphism of the glucocorticoid receptor locus and hyperinsulinaemia in obese women. 136 60

The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.
Brain Res Mol Brain Res 1992 Dec
PMID:Hypothalamic neuropeptide expression after food restriction in Zucker rats: evidence of persistent neuropeptide Y gene activation. 136 27

Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.
Mol Cell Biochem 1992 Aug 18
PMID:Genetic aspects of susceptibility to obesity and related dyslipidemias. 151 6

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.
Environ Mol Mutagen 1992
PMID:Clastogenic effect of fenfluramine in mice bone marrow cells in vivo. 160 Sep 59

Neuropeptide Y (NPY) is an important hypothalamic regulator of feeding behavior. In this study we have investigated the regulation of the expression of preproNPY mRNA in male obese and lean Zucker rats by in situ hybridization. These animals represent a model of genetic obesity with hyperphagia, hyperinsulinemia and altered endocrine functions. Obese Zucker rats, treated for 12 days with 0.9% saline, had about 210% higher level of basal preproNPY mRNA expression in the arcuate nucleus when compared to their lean littermate controls. Repeated administrations of 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a serotonergic 5-HT1A agonist, or mifepristone, a glucocorticoid receptor antagonist, did not modify the basal expression of preproNPY mRNA in the Zucker phenotypes. The 8-OH-DPAT treatment significantly reduced hyperinsulinemia in obese Zucker rats without changing plasma glucose levels. The mifepristone treatment significantly increased plasma corticosterone levels in lean animals, but not in obese animals. The present study demonstrates enhanced expression of preproNPY mRNA in the arcuate nucleus in obese Zucker rats suggesting an involvement of NPY in the pathophysiology of the hyperphagic syndrome and genetically determined obesity in Zucker rats. Neither the antagonism of glucocorticoid receptors by mifepristone, nor repeated treatment with 8-OH-DPAT resulting in reduced insulin levels in obese Zucker rats, modified the basal expression of preproNPY mRNA in the arcuate nucleus.
Brain Res Mol Brain Res 1991 Jun
PMID:Effects of repeated administration of mifepristone and 8-OH-DPAT on expression of preproneuropeptide Y mRNA in the arcuate nucleus of obese Zucker rats. 165 93

Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one; DHA) and DHA-sulfate are abundantly produced adrenal steroids, whose serum concentrations exceed those of other adrenal steroids. Serum concentrations of DHA and DHA-sulfate, in contrast to other adrenal steroids, exhibit a progressive age-related decline. The mechanism(s) for this selective decline in serum DHA and DHA-sulfate levels and the biologic function of these steroids remain unknown. Studies examining insulin's regulation of adrenal androgens are reviewed. These studies show that experimentally-induced hyperinsulinemia lowers serum DHA and DHA-sulfate levels, and suggest that insulin reduces serum concentrations of these steroids by inhibiting production rather than by increasing clearance. Studies examining the actions of short-term pharmacologic DHA administration to young nonobese and obese men are also reviewed. These studies suggest that DHA may possess hypolipidemic and, possibly, anti-obesity properties. They have failed, however, to demonstrate any effect of DHA on tissue insulin sensitivity.
J Steroid Biochem Mol Biol 1991
PMID:Metabolism and actions of dehydroepiandrosterone in humans. 183 49


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