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

Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome.
 ...
PMID:Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex. 189 72

Although microdialysis has been available for almost two decades, it has only recently been applied in investigations of adipose tissue. The microdialysis technique enables continuous sampling of metabolites and other small molecules from the extracellular space of subcutaneous adipose tissue from intact animals or man, and the exposure of this compartment locally to metabolically active agents without causing generalized effects. To date, the method has been used to measure the steady-state interstitial levels of metabolites and to investigate the regulation of lipolysis and carbohydrate metabolism in situ in subcutaneous adipose tissue. Apart from a great potential for experimental research, the microdialysis method offers several new possibilities for clinical investigation. Because microdialysis probes are easy to implant and cause little discomfort, they may be used for continuous monitoring of glucose and glycerol (lipolysis index) in the treatment of diabetes, obesity and other disorders characterized by disturbances in lipid and carbohydrate metabolism.
 ...
PMID:Microdialysis of adipose tissue. 191 34

Yohimbine, an alpha 2-receptor antagonist, was examined for its suitability in the treatment of obesity. Twenty female obese outpatients were subjected to a 3-week low-energy diet (1,000 kcal/day), after which they were randomly allocated according to a double-blind study protocol to two treatments: 10 subjects received 5 mg yohimbine per os 4 times a day and 10 received a placebo for 3 weeks, in addition to a low-energy diet of 1,000 kcal/day. Before inclusion in the study, as well as the end of each of the 3-week treatment periods, thermogenesis (resting and exercise energy expenditure) was assessed by indirect calorimetry; serum noradrenaline concentration was taken as an index of sympathetic system activity and serum glycerol level as an index of lipolysis. Yohimbine significantly increased the mean weight loss in patients on a low-energy diet: 3.55 +/- 0.24 kg (yohimbine) vs. 2.21 +/- 0.37 kg (placebo), P less than 0.005. With yohimbine, a steady level of effort-induced energy expenditure and sympathetic system activity was maintained. No significant effect of yohimbine on lipolysis was observed under the experimental conditions of this study. In another group of 15 obese inpatients (11 women and 4 men) the influence of 15 mg yohimbine per os vs. placebo on gastric emptying of a radiolabelled solid meal was examined in a double-blind manner with the use of a gamma camera. No significant effect of yohimbine on gastric emptying was revealed--the mean gastric transit time was 42.0 +/- 0.4 min after placebo and 41.8 +/- 0.5 min after yohimbine. The results obtained warrant further research on the applicability of alpha 2-receptor inhibitory drugs as a supplementary management in the treatment of obesity.
 ...
PMID:Does yohimbine act as a slimming drug? 195 8

Animal and human studies have suggested a thermogenic synergism between ephedrine (E), a beta-agonist, and caffeine (C), an adenosine antagonist, which may be suitable for the treatment of obesity. To study this phenomenon, the thermogenic effect of single doses of oral placebo, E 10 mg, E 20 mg, C 100 mg, and C 200 mg were compared with the effects of three different combinations of E + C, 10 mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg, measured by indirect calorimetry in six healthy, lean subjects. The thermogenic effect after E + C 20 mg/200 mg was larger than that of any of the other combinations. In this dose ratio, ephedrine and caffeine exerted a supra-additive synergism, whereas the thermogenic effects of the other two combinations were only additive. The 3-hour postintake increase in systolic blood pressure after all three combinations averaged 5 to 7 mm Hg more than placebo (P less than .01), which exceeded the predicted additive effect fivefold to sevenfold. Diastolic blood pressure was not increased by E + C 20 mg/200 mg, whereas the other two combinations increased it by approximately 4 mm Hg more than placebo. E + C 20 mg/100 mg and 20 mg/200 mg increased heart rate more than placebo, while E + C 10 mg/200 mg had no effect on heart rate. As expected, all combinations increased plasma glucose, insulin, and C-peptide from their ephedrine content. No significant effects of the combinations were found on plasma lactate, glycerol, nonesterified fatty acids (NEFA), triglyceride, potassium, or sodium.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. 200 46

Factors contributing to fasting hypertriglyceridaemia were studied in 20 patients with non-insulin-dependent diabetes--nine with normal triglyceride concentrations [fasting triglyceride 0.94 (range 0.58-1.23) mmol l-1] and eleven with mild fasting hypertriglyceridaemia [fasting triglyceride 2.4 (1.82-4.0) mmol l-1]. The patients with hypertriglyceridaemia were more obese [body mass index 29.0 (24.6-33.8) vs. 25.7 (21.9-30.1) kg m-2, P less than 0.05] and demonstrated impaired glucose disposal in response to exogenous insulin at isoglycaemia [insulin sensitivity index, SIp 0.7 (0.27-2.5) vs. 2.4 (0.62-5.1) ml m-2 min per mU l-1, P less than 0.001]. Basal non-esterified fatty acid (NEFA) and glycerol concentrations were higher and were suppressed to a lesser extent during isoglycaemic hyperinsulinaemia. Fasting glucose and apolipoprotein B concentrations were higher in the hypertriglyceridaemic patients, but lipoprotein lipase activities were similar in the two groups. When the effect of obesity was removed (by weight-matching six normotriglyceridaemic with seven hypertriglyceridaemic patients) basal NEFA and glycerol concentrations and the suppression of NEFA in response to insulin remained significantly different between the two groups. We propose that defects in both the glucoregulatory and antilipolytic actions of insulin contribute to mild fasting hypertriglyceridaemia in NIDDM, and that these defects cannot be attributed solely to obesity. These disorders of insulin action may also have important implications for the postprandial metabolism of triglyceride-rich lipoproteins and hence atherogenesis.
 ...
PMID:Determinants of mild fasting hypertriglyceridaemia in non-insulin-dependent diabetes. 200 44

The metabolic development of the liver and adipose tissue was examined in 75 and 110 day fetuses from genetically obese and control sows. In the liver, glucose and palmitate utilization was influenced by both age and strain. Higher rates of glucose oxidation and palmitate oxidation and esterification were observed in the 75 day compared to the 110 day fetuses. Hepatic palmitate oxidation was greater in pre-obese than in control fetuses at both fetal ages, while hepatic palmitate esterification was greater in pre-obese than in control fetuses at 75 days of gestation only. In subcutaneous adipose tissue, de novo lipogenesis increased with age and was higher in pre-obese than in control fetuses by 110 days of gestation. At 75 days of gestation, glucose oxidation and incorporation into fatty acids was similar in adipose tissue from both strains. However, by 110 days of gestation, both basal and insulin-stimulated rates of glucose metabolism were greater in pre-obese compared to control fetuses. Palmitate esterification increased with age but was similar in pre-obese and control fetuses. Basal lipolysis was not affected by strain or age. Isoproterenol had no effect on lipolysis in the 75 day fetuses while stimulating glycerol release to a comparable degree in 110 day fetuses of both strains. This study demonstrates that metabolic differences between genetically obese and control pigs are already apparent in the pre-obese state prior to birth. Such alterations in hepatic and adipose tissue carbohydrate and lipid metabolism, which promote early lipid storage by the pre-obese fetuses, may serve as useful metabolic markers for the development of obesity.
 ...
PMID:Metabolic development of liver and adipose tissue in pre-obese and control pig fetuses. 207 14

The effects of feeding a low-protein diet (5 percent w/w) and daily exercise on the rates of substrate (futile) cycling between triglyceride and fatty acids (TG-FA cycle) were studied in rats in vivo using a radiochemical assay that involves following the incorporation of tritium from 3H-H2O into the fatty acid and glycerol moieties of triglyceride. Sixty-four rats were fed either a purified control diet (COND) consisting of 70 percent carbohydrate, 20 percent protein, 5 percent fat or an experimental low protein (LPD) diet consisting of 80 percent carbohydrate, 5 percent protein and 10 percent fat (w/w) and were either exercised six days weekly or remained sedentary for six weeks. Both LPD and exercise training (EXT) were found to increase significantly the rate of TG-FA substrate cycling above the rates observed in dietary and sedentary control groups. The LPD increased significantly the rate of cycling in interscapular brown adipose (IBAT), while adipose (WAT) and diaphragm muscle. EXT increased the rates of substrate cycling in soleus, heart, and diaphragm muscle and WAT. Rate of cycling in cardiac or skeletal muscle was one-twentieth that found in adipose tissue. There were also sex differences in the rate of substrate cycling. Substrate cycling in soleus and heart muscle of male animals were consistently higher than respective female treatment groups. Sedentary and EXT LPD animals weighed significantly less than but consumed a similar amount of food to the respective COND animals. These data provide the first in vivo evidence that the rate of substrate cycling can be increased by diet or by exercise training. The possible importance of TG-FA and other substrate cycles on efficiency of energy metabolism and etiology of obesity are discussed.
 ...
PMID:Effects of diet and exercise on the in vivo rates of the triglyceride-fatty acid cycle in adipose tissue and muscle of the rat. 227 57

Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity.
 ...
PMID:Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. 230 16

Sustained elevations of plasma glucose and insulin concentrations follow intense (80% maximum oxygen uptake) exercise performed in the postabsorptive state. To provide insights into possible mechanisms and influence of obesity, 8 lean and 12 obese subjects [106 +/- 11% (SD) and 193 +/- 31% of reference table weight, respectively] eating previously isocaloric diets were exercised to exhaustion (7 +/- 3 min) on a cycle ergometer, then followed for 60 min of recovery. The obese subjects at rest had slightly increased plasma glucose and insulin and elevated blood glycerol concentrations. Both lean and obese subjects had little or no changes in plasma glucose or insulin during exercise, but the increases during the recovery period were greater and/or sustained longer in the obese. Such results raise the possibility of transient hepatic insulin resistance after exercise and are possibly relevant to restoration of depleted muscle glycogen. Both groups had a marked fall in plasma FFA during exercise; the reduction was sustained in the lean but not in the obese subjects. Blood glycerol increased during the recovery period to higher values in the obese than in the lean subjects. Plasma norepinephrine increased about 4-fold in both groups, returning promptly to preexercise values. In contrast, the exercise-induced increment in plasma epinephrine [values at exhaustion, 933 +/- 548 vs. 1970 +/- 787 pmol/L; P less than 0.005] was markedly attenuated in the obese subjects. Thus, the obese subjects had exercise-induced changes in glucose and inulin metabolism consistent with greater postexercise insulin resistance, despite an impaired plasma epinephrine response to intense exercise.
 ...
PMID:Metabolic responses to intense exercise in lean and obese subjects. 264 9

Generally obese and lean pigs in both the fed and fasted states were anesthetized and then acutely infused with increasing concentrations of the beta-adrenergic agonist isoproterenol. Plasma free fatty acid (FFA), blood glycerol, glucose and lactate, and heart rate were monitored during the infusion period. Data were reduced by estimating the parameters of the generalized logistic function (minimum, maximum, ED50 and slope) and subsequently analyzed to compare the lean and obese genotypes within nutritional state. Lactate data could not be fitted to this function because the upper asymptote was not approached during the experiment. The minimum plasma concentration of FFA tended (P less than .1) to be less in obese than in lean pigs. The maximum, ED50 and slope for the responses of FFA were similar for obese and lean pigs in fed pigs and in fasted pigs. In fed pigs, the minimum glycerol concentration was greater in obese than in lean pigs, and the ED50 for heart rate tended to be lower in lean than in obese pigs. All other estimated parameters for the variables were similar in fed obese and lean pigs. In fasted pigs, the maximum glucose concentration was greater in obese than in lean pigs. All other parameters for the variables were similar in fasted obese and lean pigs. The results suggest that there was no major defect in lipid mobilization in these obese pigs (only a lower minimum FFA concentration was detected) and that an increased maximum blood glucose concentration in the fasting state might contribute to the obesity.
 ...
PMID:Lipid mobilization by obese and lean pigs infused with the beta-adrenergic agonist isoproterenol. 279 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>