Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro experiments suggest that stimulation of lipolysis by catecholamines in adipocytes depends on the energy status of these cells. We tested whether mitochondrial uncoupling proteins (UCPs) that control the efficiency of ATP production could affect lipolysis and noradrenaline signalling in white fat in vivo. The lipolytic effect of noradrenaline was lowered by ectopic UCP1 in white adipocytes of aP2-Ucp1 transgenic mice, overexpressing the UCP1 gene from the aP2 gene promoter, reflecting the magnitude of UCP1 expression, the impaired stimulation of cAMP levels by noradrenaline and the reduction of the ATP/ADP ratio in different fat depots. Thus only subcutaneous but not epididymal fat was affected. UCP1 also down-regulated the expression of hormone-sensitive lipase and lowered its activity, and altered the expression of trimeric G-proteins in adipocytes. The adipose tissue content of the stimulatory G-protein alpha subunit was increased while that of the inhibitory G-protein alpha subunits decreased in response to UCP1 expression. Our results support the idea that the energy status of cells, and the ATP/ADP ratio in particular, modulates the lipolytic effects of noradrenaline in adipose tissue in vivo. They also demonstrate changes at the G-protein level that tend to overcome the reduction of lipolysis when ATP level in adipocytes is low. Therefore, respiratory uncoupling may exert a broad effect on hormonal signalling in adipocytes.
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PMID:Impaired noradrenaline-induced lipolysis in white fat of aP2-Ucp1 transgenic mice is associated with changes in G-protein levels. 1202 79

Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK) is a major aromatic compound of red raspberry (Rubus idaeus). The structure of RK is similar to the structures of capsaicin and synephrine, compounds known to exert anti-obese actions and alter the lipid metabolism. The present study was performed to clarify whether RK helps prevent obesity and activate lipid metabolism in rodents. To test the effect on obesity, our group designed the following in vivo experiments: 1) mice were fed a high-fat diet including 0.5, 1, or 2% of RK for 10 weeks; 2) mice were given a high-fat diet for 6 weeks and subsequently fed the same high-fat diet containing 1% RK for the next 5 weeks. RK prevented the high-fat-diet-induced elevations in body weight and the weights of the liver and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric). RK also decreased these weights and hepatic triacylglycerol content after they had been increased by a high-fat diet. RK significantly increased norepinephrine-induced lipolysis associated with the translocation of hormone-sensitive lipase from the cytosol to lipid droplets in rat epididymal fat cells. In conclusion, RK prevents and improves obesity and fatty liver. These effects appear to stem from the action of RK in altering the lipid metabolism, or more specifically, in increasing norepinephrine-induced lipolysis in white adipocytes.
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PMID:Anti-obese action of raspberry ketone. 1586 4

Chronic ethanol consumption disrupts G protein-dependent signaling pathways in rat adipocytes. Because lipolysis in adipocytes is regulated by G protein-mediated cAMP signal transduction, we hypothesized that cAMP-regulated lipolysis may be vulnerable to long-term ethanol exposure. Male Wistar rats were fed a liquid diet containing ethanol as 35% of total calories or pair-fed a control diet that isocalorically substituted maltose dextrins for ethanol for 4 wk. Lipolysis was measured by glycerol release over 1 h with or without agonists in adipocytes isolated from epididymal fat. Chronic ethanol feeding decreased beta-adrenergic receptor-stimulated lipolysis, but had no effect on basal lipolysis. In response to beta-adrenergic activation, the early peak of cAMP accumulation was suppressed after ethanol feeding, although the basal cAMP concentration in adipocytes did not differ between pair- and ethanol-fed rats. The suppression in cAMP accumulation caused by ethanol feeding was associated with increased activity of phosphodiesterase 4. Chronic ethanol feeding also decreased beta-adrenergic receptor-stimulated protein kinase A activation and phosphorylation of its downstream proteins, perilipin A and hormone-sensitive lipase, the primary lipase-mediating lipolysis. In conclusion, these data suggest that chronic ethanol feeding increased phosphodiesterase 4 activity in adipocytes, resulting in decreased accumulation of cAMP in response to beta-adrenergic activation and a suppression of beta-adrenergic stimulation of lipolysis.
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PMID:Chronic ethanol feeding suppresses beta-adrenergic receptor-stimulated lipolysis in adipocytes isolated from epididymal fat. 1679 14

This study shows the characteristics of hormone-dependent lipolysis in white adipose tissues from corpulent spontaneously hypertensive rats (SHR/NDmc-cp(cp/cp)). The glycerol-releasing activity on addition of norepinephrine (NE) and corticotropin (ACTH) was diminished in slices of epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats compared with those from Wistar Kyoto rats and lean spontaneous hypertensive rats (SHR/NDmc-cp(+/+)). 8-Bromo-cyclic adenosine monophosphate had a slight effect on lipolysis in epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats, and addition of NE and ACTH resulted in a slight accumulation of cyclic adenosine monophosphate in epididymal adipose tissue from cp/cp rats. Therefore, the alteration of hormone-dependent lipolysis-related genes was analyzed using quantitative real-time polymerase chain reaction. It was found that the expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin messenger RNAs was limited in epididymal, retroperitoneal, mesenteric, and subcutaneous adipose tissues from cp/cp rats compared with +/+ rats. These results indicate that in white adipose tissue from cp/cp rats, the diminished lipolytic response to NE and ACTH may be caused by impaired expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin.
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PMID:Characteristics of lipolysis in white adipose tissues of SHR/NDmc-cp rats, a model of metabolic syndrome. 1751 19

The aim of the present study was to examine the effect of 8 weeks of voluntary wheel running on the gene expression, at the protein level, of 2 enzymes involved in lipogenesis (fatty acid synthase [FAS] and diacylglycerol acyl transferase 1), 2 proteins involved in lipolysis (hormone-sensitive lipase [HSL] and perilipin), and 3 transcription factors mediating the induction of genes involved in lipid metabolism (the alpha, gamma, and delta members of the peroxisome proliferator-activated receptor, or PPAR, family) in rat liver, gastrocnemius muscle, epididymal fat, and subcutaneous fat. Proteins were measured through Western blot analysis in the tissues of 11 trained and 14 untrained rats. The trained rats had lower FAS in the liver; higher FAS, HSL, and perilipin in epididymal fat; and higher HSL in subcutaneous fat. In addition, the trained rats had higher total protein concentrations in both fat depots. No significant differences in the liver, muscle, or adipose tissue PPAR contents were found between groups. However, the DNA binding activity of PPARgamma, measured through an enzyme immunoassay-based method, was higher in both fat depots of the trained rats. Our findings suggest that long-term wheel running had significant effects on the concentrations of proteins playing key roles in lipogenesis and lipolysis in rat liver and adipose tissue. These effects may be due to PPAR activation rather than induction, rendering the transcriptional regulation of target genes more economical and flexible. The activation of PPARgamma with exercise may mediate its beneficial effect on insulin sensitivity.
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PMID:Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue. 1761 46

We investigated the effect of exercise before or after refeeding on cell size and on the expression of several messenger RNAs (mRNAs) involved in lipolysis and lipogenesis in fasted rat epididymal adipocytes. Fasting for 65 hours reduced the diameter of adipocytes to 72.0 microm from 78.4 microm in fed control rats, whereas refeeding for 1 or 2 days restored adipocyte size to 74.0 or 75.8 microm, respectively. Exercise before or after refeeding blocked refeeding-induced restoration of adipocyte size and led to adipocyte size similar to that observed after fasting. Fasting dramatically reduced expression of the fatty acid synthase mRNA, although expression of this gene returned to the control level after refeeding. However, exercise after but not before refeeding inhibited recovery of the expression of fatty acid synthase mRNA resulting from refeeding. In contrast, exercise before but not after refeeding led to enhanced expression of mRNAs encoding the hormone-sensitive lipase and beta(3)-aderenoceptor. Thus, exercise before or after refeeding prevents refeeding-induced restoration of adipocyte size after fasting via different pathways. Exercise before and after refeeding enhanced the expression of lipolytic mRNAs or inhibited the expression of lipogenic mRNAs, respectively.
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PMID:Exercise before or after refeeding prevents refeeding-induced recovery of cell size after fasting with a different pattern of metabolic gene expressions in rat epididymal adipocytes. 1769 72

Dermcidin (DCD), an antimicrobial peptide that is secreted by sweat glands, is reportedly a human homolog of mouse proteolysis-inducing factor. This study was conducted to investigate the effect of DCD on body fat mobilization. The expression level of DCD in the livers of Ad-DCD-injected mice was higher than in those of Ad-beta-galactosidase (Ad-beta-gal)-injected mice 7 days after injection. In addition, injection with the Ad-DCD virus led to decreased body weight and epididymal fat mass when compared with controls. The plasma triglyceride level was decreased, whereas the free fatty acid and glycerol levels were increased in the Ad-DCD-injected group. Epididymal adipose tissues obtained from Ad-DCD-injected mice consisted of smaller adipocytes than tissues obtained from Ad-beta-gal-injected mice. The gene expression profiles revealed an upregulation of hormone-sensitive lipase and adipose fatty acid-binding protein, both of which are involved in adipocyte lipolysis, in Ad-DCD-injected mice, and this lipolytic effect of DCD paralleled the increase of circulating tumor necrosis factor-alpha (TNF-alpha) level that was observed. The perilipin levels in adipose tissue were decreased in Ad-DCD-injected mice when compared with those of the control mice. Taken together, these results suggest that DCD-mediated body fat reduction might occur as a result of TNF-alpha-induced downregulation of perilipin in adipose tissue.
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PMID:Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice. 1846 79

Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.
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PMID:Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction. 1850 80

This study was designed to investigate the effects of prolonged activation of AMP-activated protein kinase (AMPK) on lipid partitioning and the potential molecular mechanisms involved in these processes in white adipose tissue (WAT). Rat epididymal adipocytes were incubated with 5'-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside (AICAR;0.5 mM) for 15 h. Also, epididymal adipocytes were isolated 15 h after AICAR was injected (i.p. 0.7 g/kg body weight) in rats. Adipocytes were utilized for various metabolic assays and for determination of gene expression and protein content. Time-dependent in vivo plasma NEFA concentrations were determined. AICAR treatment significantly increased AMPK activation, inhibited lipogenesis, and increased FA oxidation. This was accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARdelta, and PPARgamma-coactivator-1alpha (PGC-1alpha) mRNA levels. Lipolysis was first suppressed, but then increased, both in vitro and in vivo, with prolonged AICAR treatment. Exposure to AICAR increased adipose triglyceride lipase (ATGL) content and FA release, despite inhibition of basal and epinephrine-stimulated hormone-sensitive lipase (HSL) activity. Here, we provide evidence that prolonged AICAR-induced AMPK activation can remodel adipocyte metabolism by upregulating pathways that favor energy dissipation versus lipid storage in WAT. Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL.
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PMID:Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. 1905 Mar 16

This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of lipolysis in visceral (VC) and subcutaneous (SC) rat adipocytes and the molecular mechanisms involved in this process. VC (epididymal and retroperitoneal) and SC (inguinal) adipocytes were isolated from male Wistar rats (160-180 g). Adipocytes were incubated either in the absence or in the presence of the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR, 0-500 micromol/l). AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, basal and epinephrine-stimulated (100 nmol/l) glycerol release, and hormone-sensitive lipase (HSL) phosphorylation and activity were determined. AICAR-induced (500 micromol/l) AMPK activation inhibited basal glycerol release by approximately 42, 41, and 44% in epididymal, retroperitoneal, and inguinal adipocytes, respectively. Epinephrine-stimulated glycerol release was almost completely prevented by AICAR treatment in adipocytes from all fat depots. The AMPK inhibitor compound C (20 micromol/l) prevented AICAR-induced phosphorylation of AMPK and significantly increased basal (approximately 1.3-, 1.4-, and 1.7-fold) and epinephrine-stimulated (approximately 1.3-, 1.2-, 1.4-fold) glycerol release in epididymal, retroperitoneal, and inguinal adipocytes, respectively. AICAR increased phosphorylation of HSL(Ser565) and inhibited epinephrine-induced phosphorylation of HSL(Ser563) and HSL(Ser660). This was also accompanied by a 73% reduction in epinephrine-stimulated HSL activity. Compound C prevented the phosphorylation of HSL(Ser565) induced by AICAR and partially prevented the inhibitory effect of this drug on basal and epinephrine-stimulated lipolysis in adipocytes in VC and SC fat depots. In summary, despite different fat depots eliciting distinct rates of lipolysis, acute AICAR-induced AMPK activation suppressed HSL phosphorylation/activation and exerted similar antilipolytic effects on both VC and SC adipocytes.
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PMID:Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation. 1921 74


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