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)

Recently, adipose triglyceride lipase (ATGL, also called desnutrin and calcium-independent phospholipase A2 [iPLA(2)] zeta) was isolated as a novel adipose-expressed triglyceride lipase which is downregulated in obesity and may contribute to obesity-associated metabolic disorders such as hyperlipidemia and insulin resistance. To clarify expression and regulation of this fat-derived lipase, ATGL mRNA was measured in 3T3-L1 adipocytes by quantitative real-time reverse transcription-polymerase chain reaction after treatment with isoproterenol, tumor necrosis factor (TNF) alpha, insulin, and growth hormone (GH) which have been shown to influence lipolysis and insulin sensitivity profoundly. Interestingly, treatment of adipocytes with 100 nM isoproterenol, 30 ng/ml TNF alpha, and 100 nM insulin for 16 h significantly decreased ATGL mRNA to 74%, 17%, and 49% of control levels, respectively. GH did not influence ATGL synthesis. The effect of isoproterenol, TNFalpha, and insulin on ATGL expression was time- and dose-dependent. Similarly, HSL mRNA was downregulated by the three hormones. Furthermore, signaling studies suggested that activation of Gs-protein-coupled pathways by forskolin and cholera toxin is sufficient to significantly downregulate ATGL mRNA. Moreover, p44/42 mitogen-activated protein kinase appears to partly mediate the negative effect of insulin but not TNFalpha on ATGL. Taken together, downregulation of ATGL by isoproterenol, TNFalpha, and insulin might contribute to dysregulated expression and function of this lipase in obesity, hyperlipidemia, and insulin resistance.
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PMID:Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. 1600 85

Energy homeostasis, a fundamental property of all organisms, depends on the ability to control the storage and mobilization of fat, mainly triacylglycerols (TAG), in special organs such as mammalian adipose tissue or the fat body of flies. Malregulation of energy homeostasis underlies the pathogenesis of obesity in mammals including human. We performed a screen to identify nutritionally regulated genes that control energy storage in the model organism Drosophila. The brummer (bmm) gene encodes the lipid storage droplet-associated TAG lipase Brummer, a homolog of human adipocyte triglyceride lipase (ATGL). Food deprivation or chronic bmm overexpression depletes organismal fat stores in vivo, whereas loss of bmm activity causes obesity in flies. Our study identifies a key factor of insect energy homeostasis control. Their evolutionary conservation suggests Brummer/ATGL family members to be implicated in human obesity and establishes a basis for modeling mechanistic and therapeutic aspects of this disease in the fly.
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PMID:Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila. 1605 74

We describe the case of a woman who had two penroperative hypertensive crises that may have been due to her use of phentermine, a little-known sympathomimetic anti-obesity medication. The currently available anti-obesity medications are discussed: phentermine, diethylpropion, and sibutramine; all of which are sympathomimetics possessing noradrenaline and serotonin reuptake inhibitor activity. These medications should be discontinued one week preoperatively and have potential interactions with tramadol and antidepressants. The drug orlistat inhibits gastrointestinal lipase and may lead to fat soluble vitamin (A, D, E, and K) deficiency, so consideration should be given to checking coagulation status preoperatively.
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PMID:Phentermine and anaesthesia. 1611 98

The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity.
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PMID:Adipocyte lipases and defect of lipolysis in human obesity. 1624 44

The aim of the present study was to assess the effects of peanut (Arachis hypogaea L.) shell extracts (PSE) on lipases and to evaluate its potential development for the treatment of obesity. The peanut shells were extracted in 95% ethanol, and the extracts were screened for inhibitory effects on pancreatic lipase (PL) and lipoprotein lipase (LPL) activities as well as on lipolysis of 3T3-L1 adipocytes. We also examined in vivo whether PSE could prevent the body weight gain induced by feeding a high-fat diet to male Wistar rats for 12 weeks. PSE inhibits a number of lipases, including PL, LPL and, possibly, hormone sensitive lipase (HSL). PSE-treated Wistar rats showed increased fecal lipid excretion respect to the control group. Body weight and body weight gain, and liver size, were significantly lower in rats fed the high-fat diet with 1% of PSE (w:w diet) than in those fed the high-fat diet alone. The rats treated with PSE showed reduced triacylglycerol content in the liver, as well as the serum glucose and insulin. The inhibitory activity of PSE on the lipid metabolic enzymes and the increase in fecal fat excretion suggests that PSE might be useful as a treatment to reduce the dietary fat absorption. The observed reduction in intracellular lipolytic activity of cultured 3T3-L1 adipocytes may reduce the levels of circulating free fatty acids. The observed effects are likely induced by more than one bioactive component of PSE. The PSE actions may, at least in part, be attributed to the inhibition of fat absorption in the digestive tract and the reduction of the adipocyte lipolysis.
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PMID:Effects of Arachis hypogaea nutshell extract on lipid metabolic enzymes and obesity parameters. 1633 40

The Clock gene is a core component of the circadian clock in mammals. We show here that serum levels of triglyceride and free fatty acid were significantly lower in circadian Clock mutant ICR than in wild-type control mice, whereas total cholesterol and glucose levels did not differ. Moreover, an increase in body weight induced by a high-fat diet was attenuated in homozygous Clock mutant mice. We also found that dietary fat absorption was extremely impaired in Clock mutant mice. Circadian expressions of cholecystokinin-A (CCK-A) receptor and lipase mRNAs were damped in the pancreas of Clock mutant mice. We therefore showed that a Clock mutation attenuates obesity induced by a high-fat diet in mice with an ICR background through impaired dietary fat absorption. Our results suggest that circadian clock molecules play an important role in lipid homeostasis in mammals.
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PMID:Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice. 1634 93

Twenty-six normal weight subjects (22 female, 4 male) were studied to determine the relationships of fasting levels of lipoprotein lipase in gluteal adipose tissue (ATLPL) and skeletal muscle (SMLPL) to body composition and body fat distribution. No relationship was found between fasting gluteal ATLPL and percent (%) body fat. There was, however, an inverse relationship between fasting SMLPL (from the vastus lateralis) and %body fat (p=0.005). A strong inverse correlation was also seen between fasting ATLPL and waist/hip ratio (p=0.0006), a measurement of body fat distribution. These relationships existed with or without the male subjects included. The tissue-specific relationships of lipoprotein lipase to body composition and body fat distribution could relate to the development of obesity or the maintenance of normal body weight by the effects of the lipase on the partitioning of lipoprotein triglyceride fatty acids.
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PMID:Tissue-specific lipoprotein lipase: relationships to body composition and body fat distribution in normal weight humans. 1635 45

The leaf of Nelumbo nucifera Gaertn. (family Nymphaeaceae) has been used for summer heat syndrome as home remedy in Japan and China, and it has recently been used to treat obesity in China. So we investigate the pharmacological mechanism of the anti-obesity effect of Nelumbo nucifera leaves extract (NNE). We examined the effect of NNE on digestive enzyme activity, lipid metabolism and theromogenesis and evaluated the effects of anti-obesity using high-fat diet-induced obesity in mice that were treated with NNE for 5 weeks. NNE caused a concentration-dependent inhibition of the activities of alpha-amylase and lipase, and up-regulated lipid metabolism and expression of UCP3 mRNA in C2C12 myotubes. NNE prevented the increase in body weight, parametrial adipose tissue weight and liver triacylglycerol levels in mice with obesity induced by a high-fat diet. UCP3 mRNA expression in skeletal muscle tended to be higher, when mice were administrated by NNE and were exercised. Therefore, NNE impaired digestion, inhibited absorption of lipids and carbohydrates, accelerated lipid metabolism and up-regulated energy expenditure. Consequently, NNE is beneficial for the suppression of obesity.
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PMID:Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. 1649 25

The evidence for the effect of polyphenol components of berries on digestive enzymes is reviewed. Anthocyanins inhibit alpha-glucosidase activity and can reduce blood glucose levels after starch-rich meals, a proven clinical therapy for controlling type II diabetes. Ellagitannins inhibit alpha-amylase activity and there is potential for synergistic effects on starch degradation after ingestion of berries such as raspberries and strawberries, which contain substantial amounts of ellagitannins and anthocyanins. A range of berry polyphenols (e.g. flavonols, anthocyanidins, ellagitannins and proanthocyanidins) can inhibit protease activities at levels which could affect protein digestion in the gastrointestinal tract. In contrast, potential for the inhibition of gastrointestinal lipase activity, a proven therapeutic target for the control of obesity through reduced fat digestion, may be limited to proanthocyanidins. Taking into account the manifold possible synergies for inhibition of starch, protein and/or lipid digestion by the spectrum of polyphenol components present within berry species, the inhibition of digestive enzymes by dietary polyphenols may represent an under-reported mechanism for delivering some of the health benefits attributed to a diet rich in fruit and vegetables.
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PMID:The inhibitory effects of berry polyphenols on digestive enzymes. 1649 5

A number of anti-obesity drugs are currently undergoing clinical development. These include: (i) centrally-acting drugs, such as the noradrenergic and dopaminergic reuptake inhibitor radafaxine, the endocannabinoid antagonist rimonabant, the selective serotonin 5-HT2c agonist APD-356, and oleoyl-estrone; (ii) drugs that target peripheral episodic satiety signals, such as glucagon-like peptide-1 (exenatide, exenatide-LAR and liraglutide), peptide YY (intranasal PYY3-36 and AC-162325) and amylin (pramlintide); (iii) drugs that block fat absorption, such as the novel lipase inhibitors cetilistat and GT-389255; and (iv) a human growth hormone fragment (AOD-9604) that increases adipose tissue breakdown. Of these, only rimonabant has got as far as completing phase III clinical trials. This review will provide an overview of the most prominent drugs currently undergoing clinical development as potential anti-obesity therapies.
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PMID:Obesity drugs in clinical development. 1662 17


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