Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity. Hypothalamic obesity in mice was induced by single injection of aurothioglucose (300 mg/kg body wt, i.p.). All the tested substances were administered during the last 10 days before decapitation (i.m., of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue.
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PMID:Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. 1181 9

Obese patients show marked impairment in spontaneous secretion as well as in the somatotroph responsiveness to all provocative stimuli. GH insufficiency in obese patients has been reported reversible after long-term diet and marked weight loss but somatotroph secretion is not restored by fasting. Among potential neuroendocrine causes, GHRH hypoactivity has been shown but it is likely that alterations in the influence of ghrelin, the gastric-derived natural ligand of the GHS-R, and or of the NPY/leptin interplay could have a role. Among metabolic alterations, the chronic elevation of FFA levels and hyperinsulinism probably have a key role in causing GH insufficiency in obesity. Despite marked GH insufficiency, total IGF-I levels are basically preserved while free IGF-I levels are even increased thus questioning real hypoactivity of GH/IGF-I axis in obesity. Peripheral GH hypersensitivity due to increased GH receptor status, hyperinsulinism and reduced IGFBP-I levels likely explain almost normal total IGF-I and increased free IGF-I levels which, in turn, probably exert an increased negative feedback action on somatotroph cells.
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PMID:Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity. 1199 78

The effects of a 3-d peripheral administration of an alpha-MSH agonist, MTII, on body weight and the expression of uncoupling proteins (UCPs) and carnitine palmitoyltransferase-1 were determined in lean and genetically obese fa/fa rats by comparing MTII-treated animals with two different control groups, one being ad libitum fed, the other pair-fed to the amount of food consumed by MTII-treated rats. MTII treatment of lean and obese rats lowered food intake and body weight, the effects being more marked in obese than in lean rats. In both groups, MTII administration suppressed the increased plasma FFA levels brought about by food restriction. In lean rats, MTII prevented the decrease in brown adipose tissue UCP1, UCP2, and UCP3 expression and muscle UCP3 occurring during food restriction. In obese animals, MTII markedly increased brown adipose tissue (7-fold) and muscle (2.5-fold) UCP3 expression. The decrease in liver carnitine palmitoyltransferase-1 elicited by food restriction in lean and obese rats was prevented by MTII administration. In summary, the effects of MTII resemble those of leptin and are more marked in obese than in lean animals, in keeping with their reported reduced endogenous melanocortin tone. Melanocortin agonists may be useful in the treatment of obesity associated with impaired leptin signaling.
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PMID:The leptin-like effects of 3-d peripheral administration of a melanocortin agonist are more marked in genetically obese Zucker (fa/fa) than in lean rats. 1202 Nov 92

Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin resistance associated with obesity and NIDDM. We tested whether these compounds counteract the insulin antagonistic effects of recombinant human GH. Male Wistar rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7), rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR). Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4 treatment groups. During the hyperinsulinemic clamp which raised plasma insulin levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along with rhGH showed comparable GDR to the control rats. These results indicated that rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted the insulin-antagonistic action of rhGH both in the liver and the peripheral tissues. DCI was effective in offsetting peripheral insulin resistance but without any effect on hepatic insulin resistance associated with rhGH treatment.
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PMID:Pharmacological treatments for GH-induced insulin resistance. 1205 20

We previously showed that a 48-h intravenous lipid infusion in rats induces pancreatic beta-cell hypersensitivity to catecholamines. Our aim was to study the lipid-related changes that may account for such hypersensitivity in pancreatic islets. We show here that a 48-h increase in plasma FFA alters the binding characteristics of beta-cell alpha2 adrenoceptors in rats. Lipid infusion decreases pancreatic norepinephrine (NE) turnover rate by 28%, reflecting a reduction of pancreatic NE stores. Following lipid infusion, the density of alpha2 adrenoceptor binding sites is significantly lower and receptor affinity higher, both in islet homogenates (by three- and fivefold, respectively) and isolated whole beta-cells (by two- and sixfold, respectively). These changes correlate with the elevated insulin response to glucose found in lipid-infused rats. We also found a modification of islet phospholipid content, particularly in phosphoethanolamine species containing infused FA such as palmitate, oleate, stearate, and linoleate. This may account for the modifications in receptor affinity. These results suggest that hyperlipidemia-associated pathologies such as diabetes and obesity not only may result from alterations of metabolic pathways but also may be a consequence of early modifications in nervous firing rates and signal transduction pathways.
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PMID:Pancreatic beta-cell alpha2A adrenoceptor and phospholipid changes in hyperlipidemic rats. 1205 93

We determined whether interindividual variation in hepatic insulin sensitivity could be attributed to variation in liver fat content (LFAT) independent of obesity. We recruited 30 healthy nondiabetic men whose LFAT (determined by proton spectroscopy); intraabdominal, sc, and total (determined by magnetic resonance imaging) fat; and insulin sensitivity of endogenous glucose rate of production (R(a)) and suppression of serum FFA [euglycemic insulin clamp combined with [3-(3)H]glucose (0-300 min); insulin infusion rate, 0.3 mU/kg.min, 120-300 min] were measured. The men were divided into groups of low (mean +/- SD, 1.7 +/- 0.2%) and high (10.5 +/- 2.0%) LFAT based on their median fat content. The low and high LFAT groups were comparable with respect to age (44 +/- 2 vs. 42 +/- 2 yr), body mass index (25 +/- 1 vs. 26 +/- 1 kg/m(2) ), waist to hip ratio (0.953 +/- 0.013 vs. 0.953 +/- 0.013), maximal oxygen uptake (35.6 +/- 1.5 vs. 33.5 +/- 1.5 ml/kg.min), and intraabdominal, sc, and total fat. The high compared with the low LFAT group had several features of insulin resistance, including fasting hyperinsulinemia (7.3 +/- 0.6 vs. 5.3 +/- 0.6 mU/liter; P < 0.02, high vs. low LFAT) hypertriglyceridemia (1.4 +/- 0.2 vs. 0.9 +/- 0.1 mmol/liter; P < 0.02), a low high density lipoprotein (HDL) cholesterol concentration (1.4 +/- 0.1 vs. 1.6 +/- 0.1 mmol/liter; P < 0.05), and a higher ambulatory 24-h systolic blood pressure (130 +/- 3 vs. 122 +/- 3 mm Hg; P < 0.05). Basal glucose R(a) and serum FFA were comparable between the groups, whereas insulin suppression of glucose R(a) [51 +/- 8 vs. 20 +/- 12 mg/m(2).min during 240-300 min (P < 0.05) or -55 +/- 7 vs. -85 +/- 12% below basal (P < 0.05, high vs. low LFAT)] and of serum FFA (299 +/- 33 vs. 212 +/- 13 micromol/liter; 240-300 min; P < 0.02) were impaired in the high compared with the low LFAT group. Insulin stimulation of glucose Rd were comparable in the men with high LFAT (141 +/- 12 mg/m(2).min) and those with low LFAT (156 +/- 14 mg/m(2).min; P = NS). Fat accumulation in the liver is, independent of body mass index and intraabdominal and overall obesity, characterized by several features of insulin resistance in normal weight and moderately overweight subjects.
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PMID:Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. 1210 93

The relationship between obesity and type 2 diabetes has been known for decades and the recent important increase in such diseases represents a major medical problem worldwide. Several prospective studies present both impaired insulin release and insulin resistance as the major factors for the development of type 2 diabetes. The factor that dominates in obesity is the permanent elevation of plasma FFA and the predominant utilization of lipids by the muscle inducing a diminution of glucose uptake and, therefore, insulin resistance. The rise in insulin secretion appears to be a compensatory mechanism that responds to the increased levels of circulating glucose. The fall in insulin secretion occurs as a late phenomenon. The present review aims at analysing the mechanisms that lead human obesity to type 2 diabetes and using the pathophysiological information for the prevention of diabetes. The partial reversibility of the evolution of obesity towards diabetes is well demonstrated today by lifestyle changes and multidisciplinary weight loss programs.
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PMID:Pathways from obesity to diabetes. 1217 27

The aim of the study was to examine the allelic frequency of the -3826A > G mutation of UPC1 in patients with familiar obesity and to investigate putative association of this polymorphism with metabolic disorders. One hundred and eighteen overweight /obese patients participated in the study. The UCP1 polymorphism was determined by RFLP. Glucose, lipid, insulin and leptin levels were measured both during OGTT and OLTT. The majority of patients had a homozygous A/A genotype (51,38%), while 14,68% had a G/G genotype. We found no significant association of the G allele with either BMI or glucose tolerance. Patients with the homozygous G/G genotype had significantly higher fasting levels of TG (p < 0.04) and decreased levels of HDL-cholesterol (p = 0,004). They also had an increased concentration of FFA and the rise of TG levels during the OLTT compared to controls was significant (p = 0,058). In addition, the carriers of the G/G genotype had the lowest insulin levels both during OGTT and OLTT. In our study we have demonstrated that the -3826A > G polymorphism of UCP1 does not play a major role in the development of obesity and/or disturbances of glucose metabolism. However, the increased levels of TG and FFA and decreased levels of HDL observed in carriers of the G allele suggest FFA-induced impairment of the HDL turnover and disturbance of the beta-cell function, both of which are risk factors for endothelial injury.
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PMID:Correlation of the -3826A >G polymorphism in the promoter of the uncoupling protein 1 gene with obesity and metabolic disorders in obese families from southern Poland. 1237 83

Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because "normal" FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean and obese adults (25 women). Resting energy expenditure (REE), but not body composition, predicted most of the interindividual variation in FFA release. There was a significant, positive linear relationship between palmitate release and REE; however, women released approximately 40% more FFA than men relative to REE. Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women. Glucose release rates were not different in men and women whether related to REE or fat free mass. These findings indicate that nonoxidative FFA clearance is greater in women than in men. This could be an advantage at times of increased fuel needs. We conclude that "normal" adipose tissue lipolysis is different in men and women and that the fuel export role of adipose tissue in obesity will need to be reassessed.
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PMID:Energy expenditure, sex, and endogenous fuel availability in humans. 1267 Oct 47

We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we investigate the association of GLUT4 expression with the intracellular triglyceride (TG) content in the same muscle fibres and with plasma lipid parameters. We used histochemistry and stereology to study the relationship between TG content and GLUT4 expression in muscle fibres from obese, obese type 2 diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (p<0.05). We found an increased TG density in slow twitch fibres of obese diabetic subjects compared to obese (p<0.05) and lean controls (p<0.008). Intracellular TG densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced GLUT4 expression. The GLUT4 expression was not associated with an increased intracellular triglyceride content or with increased plasma FFA levels. Thus, intracellular TG content and circulating FFA may not influence glucose transport directly through GLUT4 expression.
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PMID:GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance? 1271 91


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