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 presence of glycerokinase has been demonstrated in human omental and subcutaneous adipose tissue. The enzyme reaction showed a linear time course for 5 min at 30 C and pH optima at pH 7.6 and 9.0. Saturation of the enzyme was observed at 1.8 mM adenosine triphosphate (ATP) and the double reciprocal plot of activity vs. ATP concentration was nonlinear giving two apparent Km values of 0.094 and 0.518 mM. The apparent Km for glycerol, 0.112 mM, was obtained from a linear double reciprocal plot, and the enzyme was saturated at about 0.4 mM glycerol. The activity of glycerokinase in human adipose tissue excised under general anaesthesia was low and was unrelated to adipose cell size or the degree of obesity of the subject from whom the fat was obtained.
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PMID:Glycerokinase in human adipose tissue. 1 78

Glycerokinase activity in isolated fat cells was elevated in both Ob/Ob and Db/Db mice in comparison to their lean controls and this elevation was associated with obesity, hyperinsulinemia and hyperglycemia. In the other forms of acquired and genetic obesity in the rats and mice studied (also associated with hyperinsulinemia), adipose tissue glycerokinase activity was not elevated in comparison to lean control groups when expressed on a mg protein basis. It is concluded that the elevated glycerokinase activity is not due to the specific Db or Ob mutation, but is secondary to the obesity and hyperinsulinemia interacting with the similar genetic background in the C57BL/KsJ and the C57BL/6J mouse strains.
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PMID:Adipose tissue glycerokinase activity in genetic and acquired obesity in rats and mice. 16 46

A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.
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PMID:Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances. 16 85

In this study of spontaneous obesity of pigs, specific metabolic shifts were observed, which explain an increase in fat deposition. Liver tissue utilization of pyruvate and glucose for oxidation and lipogenesis showed no significant difference between lean and obese pigs. Adipose tissue utilization of glucose, acetate and glycerol for triglyceride and fatty acid synthesis was greater in obese pigs than lean pigs (P less than 0.01). No significant difference in leucine incorporation into lipid fractions was found. Of the substrates utilized, glucose supplied 86 and 94% of the glyceride-glycerol synthesized in lean and obese pigs, respectively. Glycerol was not a major contributor to glyceride-glycerol synthesis (3.5 to 5.5%), in spite of the presence of adipose tissue glycerokinase. An increase (P less than 0.05) in alanine incorporation into glucose was observed in liver tissue from obese pigs. In general, the levels of enzymes activities associated with gluconeogenesis, glycolysis, and lipogenesis supported the findings of in vitro utilization of these substrates.
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PMID:A comparison of the enzyme levels and the in vitro utilization of various substrates for lipogenesis in pair-fed lean and obese pigs. 125 Aug 52

The activity of the enzyme glycerokinase is low in mammalian adipose tissue, but high in certain forms of genetic obesity in rats and mice. This study was undertaken to determine if obese human subjects had higher glycerokinase activity than normal-weight subjects. Seventy-three randomly selected patients undergoing abdominal surgery were studied. Subcutaneous and omental adipose tissue was removed during surgery and the activity of the enzyme glycerokinase was measured in vitro under optimal conditions. The following observations were made: (1) the mean activity, when expressed per microgram DNA, was significantly (P less than 0.05) higher in obese subjects at both sites, yet no direct correlation to the degree of obesity was found; (2) the individual activity in morbidly obese patients undergoing gastroplasty correlated inversely with the rate of postoperative weight loss (r = -0.58, P less than 0.05); (3) glycerokinase activity was directly related (r = 0.59, P less than 0.01) to the rate of spontaneous glycerol release, and inversely related (r = -0.51, P less than .025) to the stimulation in glycerol release by norepinephrine; (4) the ratio glycerokinase/lipoprotein lipase in omental adipose tissue correlated with the degree of obesity (r = 0.43, P less than 0.05); (5) in nondiabetic male obese adults, the glycerokinase activity in subcutaneous adipose tissue inversely correlated with age (P = 0.05) and (6) the glycerokinase activity had two apparent Km values in three obese patients, in which it was studied kinetically. It is concluded that a small subsection of the obese population have a high potential for glycerol phosphorylation. In these individuals, weight loss is more difficult since they tend to reutilize the glycerol formed by lipolysis and net glycerokinase activity in their adipose tissue may reflect variations in lipid turnover.
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PMID:Glycerokinase activity in human adipose tissue as related to obesity. 609 31

The effect of a four-week experiment on ten fa/fa Zucker rats (aged seven weeks at the beginning) fed on a lipid-rich diet (HL: 31 per cent w/w lipids, 45.6 per cent starch) was compared to that of a control diet (C: 10 per cent lipids, 66 per cent starch) on control Fa/- rats using a special pair-feeding apparatus that made it possible to obtain an identical intake rhythm. Energy level of the intake was significantly higher for the HL diet than for the C diet. At the end of the experiment, fa/fa rats remained obese and hyperlipemic, and still showed liver steatosis. With equal energy levels ingested, the obesity of fa/fa rats was comparable for both diets; hypertriglyceridemia and hypercholesterolemia were identical for both diets. When compared to the C diet, the HL diet modified neither their obesity nor their hyperlipemia. Obese rat liver on the HL diet showed lower levels for triacylglycerols, cholesterol, GGT, ALT, LDH and aldolase activities, while hepatic glycerol kinase and AST activities were higher than and comparable to, respectively, the C diet. Thus the HL diet led to a decreased liver steatosis for fa/fa rats as compared to the C diet.
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PMID:Influence of diet composition on obesity, hyperlipemia and liver steatosis in Zucker fa/fa rats pair-fed with Zucker Fa/- rats. 637 17

Thiazolidinediones are used to treat type 2 diabetes mellitus because they decrease plasma glucose, insulin, triglyceride, and fatty acid levels. Thiazolidinediones are agonists for peroxisome proliferator-activated receptor gamma, a nuclear receptor that is highly expressed in fat tissue. We identify glyceroneogenesis as a target of thiazolidinediones in cultured adipocytes and fat tissues of Wistar rats. The activation of glyceroneogenesis by thiazolidinediones occurs mainly in visceral fat, the same fat depot that is specifically implicated in the progression of obesity to type 2 diabetes. The increase in glyceroneogenesis is a result of the induction of its key enzyme, phosphoenolpyruvate carboxykinase, whose gene expression is peroxisome proliferator-activated receptor gamma-dependent in adipocytes. The main role of this metabolic pathway is to allow the re-esterification of fatty acids via a futile cycle in adipocytes, thus lowering fatty acid release into the plasma. The importance of such a fatty acid re-esterification process in the control of lipid homeostasis is highlighted by the existence of a second thiazolidinedione-induced pathway involving glycerol kinase. We show that glyceroneogenesis accounts for at least 75% of the whole thiazolidinedione effect. Because elevated plasma fatty acids promote insulin resistance, these results suggest that the glyceroneogenesis-dependent fatty acid-lowering effect of thiazolidinediones could be an essential aspect of the antidiabetic action of these drugs.
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PMID:Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. 1264 61

Although recent evidence suggests that leptin can directly regulate a wide spectrum of peripheral functions, including fat metabolism, genetic examples are still needed to illustrate the physiological significance of direct actions of leptin in a given peripheral tissue. To this end, we used a technical knock-out approach to reduce the expression of leptin receptors specifically in white adipose tissue. The evaluation of leptin receptor reduction in adipocytes was based on real time PCR analysis of the mRNA levels, Western blot analysis of the proteins, and biochemical analysis of leptin signaling capability. Despite a normal level of leptin receptors in the hypothalamus and normal food intake, mutant mice developed increased adiposity, decreased body temperature, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and insulin sensitivity, as well as elevated hepatic and skeletal muscle triglyceride levels. In addition, a variety of genes involved in regulating fat and glucose metabolism were dysregulated in white adipose tissue. These include tumor necrosis factor-alpha, adiponectin, leptin, fatty acid synthase, sterol regulatory element-binding protein 1, glycerol kinase, and beta3-adrenergic receptor. Furthermore, the mutant mice are significantly more sensitive to high fat feeding with regard to developing obesity and severe insulin resistance. Thus, we provide a genetic model demonstrating the physiological importance of a peripheral effect of leptin in vivo. Importantly, this suggests the possibility that leptin resistance at the adipocyte level might be a molecular link between obesity and type 2 diabetes.
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PMID:Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance. 1292 33

In adipocytes, hydrolysis of triglycerides results in the release of free fatty acids and glycerol. Aquaporin 7 (AQP7), a member of aquaglyceroporins, is known to permeabilize glycerol and water. We recently generated Aqp7-knockout (KO) mice and demonstrated that such mice have low plasma glycerol levels and impaired glycerol release in response to beta3-adrenergic agonist, suggesting that AQP7 acts as a glycerol gateway molecule in adipocytes for the efficient release of glycerol in vivo. Although there was no difference in body weight between WT and KO mice until 10 weeks of age, here we found that KO mice developed adult-onset obesity. The body weight and fat mass increased significantly in KO mice compared with WT mice after 12 weeks of age. Adipocytes of KO mice were large and exhibited accumulation of triglycerides compared with WT mice. The KO mice developed obesity and insulin resistance even at a young age after consumption of high-fat/high-sucrose diet. We demonstrated the enhanced glycerol kinase enzymatic activity in Aqp7-KO and -knockdown adipocytes. A series of our results indicate that AQP7 disruption elevates adipose glycerol kinase activity, accelerates triglycerides synthesis in adipocytes, and, finally, develops obesity.
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PMID:Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. 1604 37

In this study, we examined whether the increased availability of lipids in blood resulting from two types of diet manipulation regulated metabolic gene expression in the skeletal muscle of rats. Feeding for 4 wk on an isocaloric-sucrose or a hypercaloric-fat diet increased plasma TAG in the fed condition by increments of 70 and 40%, respectively, and increased fasting insulinemia (approximately 3-fold) compared with a starch diet. The fat diet impaired glucose tolerance and caused obesity, whereas sucrose-fed rats maintained their normal weight. We analyzed the expression of genes that regulate the exogenous FA supply (LPL, FAT/CD36, FATP1), synthesis (ACC1), glucose (GLUT4, GLUT1, HK2, GFAT1, glycogen phosphorylase) or glycerol (glycerol kinase) provision, or substrate choice for oxidation (PDK4) in gastrocnemius and soleus muscles at the end of the glucose tolerance test. LPL, FAT/CD36, FATP1, PDK4, and GLUT4 mRNA as well as glycogen phosphorylase and glycerol kinase activity levels in both muscles were unchanged by the diets. Increased mRNA levels of GLUT1 (1.6- and 2.6-fold, respectively) and GFAT1 (about 1.7-fold) in gastrocnemius, and of ACC1 (about 1.5-fold) in soleus, were found in both the sucrose and fat groups. In the fat group, HK2 mRNA was also higher (1.8-fold) in the gastrocnemius. Both sucrose and saturated-fat diets prompted hyperinsulinemia and hyperlipemia in rats. These metabolic disturbances did not alter the expression of LPL, FAT/CD36, FATP1, PDK4, and GLUT4 genes or glycogen phosphorylase and glycerol kinase activity levels in either analyzed muscle. Instead, they were linked to the coordinated upregulation in gastrocnemius of genes that govern glucose uptake and the hexosamine pathway, namely, GLUT1 and GFAT1, which might contribute to insulin resistance.
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PMID:Effect of sucrose and saturated-fat diets on mRNA levels of genes limiting muscle fatty acid and glucose supply in rats. 1655 72


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