Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysfunctional cross talk between adipose tissue and liver tissue results in metabolic and inflammatory disorders. As an insulin sensitizer, rosiglitazone (Rosi) improves insulin resistance yet causes increased adipose mass and weight gain in mice and humans. Conjugated linoleic acid (CLA) reduces adipose mass and body weight gain but induces hepatic steatosis in mice. We examined the combined effects of Rosi and CLA on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed male C57Bl/6 mice. CLA alone suppressed weight gain and adipose mass but caused hepatic steatosis. Addition of Rosi attenuated CLA-induced insulin resistance and dysregulation of adipocytokines. In adipose, CLA significantly suppressed lipoprotein lipase and fatty acid translocase (FAT/CD36) mRNA, suggesting inhibition of fatty acid uptake into adipose; addition of Rosi completely rescued this effect. In addition, CLA alone increased markers of macrophage infiltration, F4/80, and CD68 mRNA levels, without inducing TNF-alpha in epididymal adipose tissue. The ratio of Bax to Bcl2, a marker of apoptosis, was significantly increased in adipose of the CLA-alone group and was partially prevented by treatment of Rosi. Immunohistochemistry of F4/80 demonstrates a proinflammatory response induced by CLA in epididymal adipose. In the liver, CLA alone induced microsteatotic liver but surprisingly increased the rate of very-low-density lipoprotein-triglyceride production without inducing inflammatory mediator-TNF-alpha and markers of macrophage infiltration. These changes were accompanied by significantly increased mRNA levels of stearoyl-CoA desaturase, FAT/CD36, and fatty acid synthase. The combined administration of CLA and Rosi reduced hepatic liver triglyceride content as well as lipogenic gene expression compared with CLA alone. In summary, dietary CLA prevented weight gain in Rosi-treated mice without attenuating the beneficial effects of Rosi on insulin sensitivity. Rosi ameliorated CLA-induced lipodystrophic disorders that occurred in parallel with rescued expression of adipocytokine and adipocytes-abundant genes.
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PMID:Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice. 1732 64

The lipogenic gene stearoyl-CoA desaturase (SCD)1 appears to be a promising new target for obesity-related diabetes, as mice deficient in this enzyme are resistant to diet- and leptin deficiency-induced obesity. The BTBR mouse strain replicates many features of insulin resistance found in humans with excess visceral adiposity. Using the hyperinsulinemic-euglycemic clamp technique, we determined that insulin sensitivity was improved in heart, soleus muscle, adipose tissue, and liver of BTBR SCD1-deficient mice. We next determined whether SCD1 deficiency could prevent diabetes in leptin-deficient BTBR mice. Loss of SCD1 in leptin(ob/ob) mice unexpectedly accelerated the progression to severe diabetes; 6-week fasting glucose increased approximately 70%. In response to a glucose challenge, Scd1(-/-) leptin(ob/ob) mice had insufficient insulin secretion, resulting in glucose intolerance. A morphologically distinct class of islets isolated from the Scd1(-/-) leptin(ob/ob) mice had reduced insulin content and increased triglycerides, free fatty acids, esterified cholesterol, and free cholesterol and also a much higher content of saturated fatty acids. We believe the accumulation of lipid is due to an upregulation of lipoprotein lipase (20-fold) and Cd36 (167-fold) and downregulation of lipid oxidation genes in this class of islets. Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of beta-cells, resulting in an increased risk of diabetes.
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PMID:Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. 1736 21

Epicardial fat is a relatively neglected component of the heart. The purpose of this review was to examine the anatomic and biochemical data on epicardial fat; to examine the relationship of epicardial fat to obesity and to explore the potential role of epicardial fat in the relationship of obesity to coronary atherothrombotic disease. Epicardial fat covers 80% of the heart's surface and constitutes 20% of total heart weight. It is present along the distribution of the coronary arteries, over the right ventricle especially along the right border, anterior surface and at the apex. There is three- to fourfold more epicardial fat associated with the right than the left ventricle. Putative physiologic functions of epicardial fat are based on observational data and include: buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, facilitating coronary artery remodelling, regulating fatty acid homeostasis in the coronary microcirculation and providing fatty acids to cardiac muscle as a local energy source in times of high demand. A considerable amount of the data on epicardial fat originates from autopsy series that have the inherent problem that conditions leading to death may have altered body composition and adiposity. With this caveat, data indicate that epicardial fat mass increases age until age 20-40 years but thereafter the amount of epicardial fat is not dependent on age. The amount of epicardial fat correlates with heart weight but the presence of myocardial ischemia and hypertrophy does not alter the ratio of epicardial fat to cardiac muscle mass. A number of properties differentiate epicardial fat from other fat depots specifically its smaller adipocytes size; different fatty acid composition, high protein content; high rates of fatty acid incorporation, fatty acid synthesis, insulin-induced lipogenesis or fatty acid breakdown; low rates of glucose utilization, low expression (mRNA) of lipoprotein lipase, stearoyl-CoA desaturase and acetyl-CoA carboxylase-alpha, and slow regression during weight loss. There is a significant direct relationship between the amount of epicardial fat and general body adiposity. Clinical imaging studies have demonstrated a strong direct correlation between epicardial fat and abdominal visceral adiposity. Several lines of evidence support a role for epicardial fat in the pathogenesis of coronary artery disease, namely the close anatomic relationship between epicardial fat and coronary arteries; the positive correlation between the amount of epicardial fat and the presence of coronary atherosclerosis and the ability of adipose tissue to secrete hormones and cytokines that modulate coronary artery atherothrombosis. Thus, epicardial fat maybe an important factor responsible for cardiovascular disease in obesity.
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PMID:Epicardial fat: properties, function and relationship to obesity. 1744 66

1,25-Dihydroxyvitamin D3, the physiologically active form of vitamin D3, exerts its functions through a receptor-mediated mechanism and plays an important role in the cell differentiation. This study investigated the effects of 1,25-dihydroxyvitamin D3 on the proliferation and differentiation of porcine preadipocyte. Stromal-vascular cells containing preadipocytes were prepared from dorsal subcutaneous adipose tissue of approximately 3-day-old Chinese male crossbred pigs. After confluence, the differentiation was induced by transferrin, dexamethasone and insulin for 2 days, and then subsequently cultured for 6 days. The cells were treated with 1,25-dihydroxyvitamin D3 during the induction of differentiation (the early phase of differentiation) or throughout the differentiation period. The terminal differentiation markers, such as glycerol-3-phosphate dehydrogenase activity and lipid accumulation were measured during the process of cultures. The treatment with 1,25-dihydroxyvitamin D3 severely affected the induction of all differentiation markers throughout the differentiation period. 1,25-Dihydroxyvitamin D3 suppressed the expression of peroxisome proliferator-activated receptor gamma mRNA and interfered with the induction of retinoid X receptor alpha mRNA. The mRNAs of the adipogenesis-related genes, lipoprotein lipase, stearoyl-CoA desaturase, phosphoenolpyruvate carboxykinase, glycerol-3-phosphate dehydrogenase and glucose transporter 4 were reduced when 1,25-dihydroxyvitamin D3 was added into differentiation medium. Also, 1,25-dihydroxyvitamin D3 inhibited preadipocyte differentiation in dose-dependent manner. These results suggested that 1,25-dihydroxyvitamin D3 inhibited porcine preadipocyte differentiation through suppressing PPAR gamma and RXR alpha mRNA expressions and then down regulating the expression of adipogenesis-related genes.
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PMID:Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of porcine preadipocyte in vitro. 1780 83

To assess the effect of lupin protein on concentrations of lipids in plasma lipoproteins and liver and hepatic mRNA concentrations of genes involved in lipid metabolism, adult rats were fed egg albumin-based diets containing either lupin protein from Lupinus albus or casein (50 g/kg) supplemented (hypercholesterolaemic) or not (normolipaemic) with a cholesterol-cholate mixture for 20 d. Lupin protein compared with casein lowered the concentrations of TAG in liver (P < 0.01) and circulating VLDL + chylomicrons (P < 0.05) of hypercholesterolaemic rats, but not of normolipaemic rats. Hepatic mRNA concentrations of genes involved in fatty acid synthesis such as sterol regulatory element-binding protein-1c, glucose-6-phosphate dehydrogenase, fatty acid synthase, stearoyl-CoA desaturase-1 and acyl-CoA:glycerol-3-phosphate acyltransferase were lower and mRNA concentrations of lipoprotein lipase, hepatic lipase and apoA5 involved in TAG hydrolysis were higher in rats fed lupin protein than in rats fed casein. These effects were stronger in hypercholesterolaemic rats than in normolipaemic rats. Hypercholesterolaemic rats fed the lupin protein had higher liver cholesterol concentrations (P < 0.01) and lower levels of LDL-cholesterol (P < 0.05) than rats fed casein. No effect of lupin protein was observed on cholesterol concentration in VLDL + chylomicrons and HDL and hepatic mRNA concentrations of genes involved in cholesterol and bile acid metabolism. In conclusion, the present study shows that lupin protein has hypotriacylglycerolaemic action possibly via down regulation of fatty acid synthesis genes and up regulation of genes involved in TAG hydrolysis. Alterations in cholesterol metabolism could not be explained on the basis of mRNA data.
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PMID:Lupin protein influences the expression of hepatic genes involved in fatty acid synthesis and triacylglycerol hydrolysis of adult rats. 1809 91

There is growing evidence that dietary proteins may interfere with lipid metabolism. We therefore examined the effects of feeding obese Zucker rats a single cell protein (SCP) with low ratios of methionine:glycine and lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and lowered the plasma transaminase levels when compared with casein-fed rats (controls). The fatty acid oxidation was increased in liver mitochondria and peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG biosynthesis were unaffected. SCP feeding affected the fatty acid composition of liver lipids and plasma, and reduced the mRNA levels of the fatty acid desaturases. The decreased gene expression of stearoyl-CoA desaturase suggested that the fatty acids were directed towards oxidation rather than esterification as TAG. The decreased mRNA levels of VLDL-receptor and lipoprotein lipase in the liver after SCP feeding suggested that the uptake of TAG-rich lipoprotein to the liver was decreased. To conclude, the reduced fatty liver by SCP feeding may be caused by the increased capacity for fatty acid beta-oxidation in the liver, combined with changed fatty acid composition and possibly a reduced hepatic clearance of circulating VLDL. An increased awareness of the effect of dietary proteins on lipid metabolism could be of relevance in future dietary treatment of non-alcoholic fatty liver disease.
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PMID:Dietary single cell protein reduces fatty liver in obese Zucker rats. 1834 5

The expression changes of genes associated with adipose metabolism and regulation of cell growth in backfat tissue at five growth stages (1, 2, 3, 4 and 5 months) of Landrace (a leaner Western breed) and Taihu pigs (a fatty indigenous Chinese breed) were measured by using pathway-focused Oligo microarray. The comparative results between two pig breeds of change ratios showed that the fold changes of 10, 6, 11, 8 and 19 genes were over two times at same month from 1 to 5 months respectively. Variance analysis (ANOVA) revealed that 25 genes in Landrace pigs showed significantly altered in expression among five growth stages (P < 0.05). Principal components analysis (PCA) revealed that angiopoietin-like 4 (ANGPTL4), cathepsin K (CTSK), isocitrate dehydrogenase 2(NADP+) (IDH2), lipoprotein lipase (LPL), malic enzyme 1 (ME1), stearoyl-CoA desaturase (SCD) and uncoupling protein 2 (UCP2) displayed distinctive expression patterns from other genes, which suggested that these genes may be subject to special regulation during the period from 1 to 5 months. K-means clustering analysis revealed that genes in Landrace pigs which showed up-regulation were mainly related to the positive regulation of fatty acid metabolism and genes in Taihu pigs which showed slight fluctuation were mainly related to the regulation of cell growth. Quantitative real-time RT-PCR was used to verify the microarray data for five modulated genes, and a good positive correlation between the two measures of expression was observed for both two pig breeds at different growth stages. These results highlight some possible candidate genes for porcine carcass and meat quality traits, reveal the expressional disciplinarian of correlative genes and provide some data on which to base further study of the dynamic balance process for fatty acid biogynthesis and hydrolyzation.
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PMID:[Developmental expression changes of specific genes in adipose tissue for different pig breeds by using pathway-focused microarray]. 1861 80

Twenty-eight Angus steers (289 kg) were finished on a high-concentrate diet (85% concentrate: 15% roughage; CONC), or endophyte-free tall fescue pastures with corn grain supplement (0.52% of BW; PC), corn oil plus soybean hull supplement (0.10% of BW corn oil plus 0.45% of BW soybean hulls; PO), or no supplement (pasture only; PA). Subcutaneous adipose tissues were processed for total cellular RNA extraction and fatty acid composition by GLC. Relative expression of genes involved in lipogenesis [fatty acid synthase (FASN), acetyl-CoA carboxylase, lipoprotein lipase, stearoyl-CoA desaturase (SCD)] and activators of transcription [(peroxisome proliferator-activated receptor-gamma), C/EBPalpha, sterol regulatory binding protein-1, signal transducer and activator of transcription-5, and Spot-14] was determined by real-time quantitative PCR. Housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase and beta-actin) expression was used in analysis to normalize expression data. Total fatty acid content was greatest (P < 0.001) for CONC and least (P < 0.001) for PA. Supplementation of grazing cattle increased (P < 0.001) total fatty acid content compared with PA, but concentrations were less (P < 0.001) than for CONC. Myristic and palmitic acid contents were greater (P < 0.001) for CONC than for PO and PC, which were greater (P < 0.001) than for PA. Stearic acid content was greater (P < 0.01) for PO than for CONC, PC, and PA. Finishing on CONC increased (P < 0.001) total MUFA content by 68% compared with PA. Corn grain supplementation increased (P < 0.001) MUFA content compared with PA; in contrast, MUFA content did not differ (P > 0.05) between PO and PA. Corn oil supplementation increased (P < 0.001) trans-11 vaccenic acid content in subcutaneous fat by 1.2-, 1.7- and 5.6-fold relative to PA, PC, and CONC, respectively. Concentrations of the cis-9, trans-11 CLA isomer were 54, 58, and 208% greater (P < 0.01) for PO than for PA, PC, and CONC, respectively. Corn grain supplementation to grazing steers did not alter (P > 0.05) the cis-9, trans-11 CLA isomer compared with PA. Oil supplementation increased (P < 0.001) linoleic acid (C18:2) content by 56, 98 and 262% compared with CONC, PC, and PA, respectively. Relative mRNA expression of SCD was upregulated (P < 0.001) by 46-, 18- and 7-fold, respectively, for CONC, PC, and PO compared with PA. Relative FASN mRNA expression was also upregulated (P = 0.004) by 9- and 5-fold, respectively, for CONC and PC compared with PA. Grain feeding, either on CONC or supplemented on pasture, upregulated FASN and SCD mRNA to increase MUFA and de novo fatty acids in subcutaneous adipose tissue. Upregulation of SCD with grain feeding and reduced tissue CLA concentrations suggest that the decreased CLA concentrations were the result of limited substrate (trans-11 vaccenic acid) availability.
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PMID:Corn oil or corn grain supplementation to steers grazing endophyte-free tall fescue. II. Effects on subcutaneous fatty acid content and lipogenic gene expression. 1902 50

Milk fat depression (MFD) is a naturally occurring condition in dairy cows where milk fat synthesis is inhibited by intermediates of ruminal biohydrogenation. One of these bioactive fatty acids (FA), trans-10, cis-12 conjugated linoleic acid (CLA), decreases milk fat synthesis through transcriptional downregulation of genes involved in mammary lipid synthesis. Energy partitioning during MFD is not well characterized because of the complexity of observing energy metabolism in ruminant animals. To investigate energy partitioning during MFD, adipose tissue biopsies were taken from 4 cows arranged in a switchback design. Treatments were control and 4-d abomasal infusion of trans-10, cis-12 CLA (7.5 g/d). CLA decreased milk fat yield by 38% and milk fat content by 34%, but yields of milk and other milk components were unchanged. In contrast to reported changes in mammary tissue, adipose tissue expression of lipid synthesis enzymes, including lipoprotein lipase, FA synthase, stearoyl-CoA desaturase, and FA binding protein 4, was increased. Expression of regulators of lipid synthesis, including sterol-response element binding protein 1, thyroid hormone responsive spot 14, and PPARgamma, also increased in adipose tissue. Thus, a CLA dose resulting in near maximal inhibition of mammary lipid synthesis resulted in increased expression of lipid synthesis-related genes in adipose tissue. A meta-analysis of intake response during CLA infusion was conducted to extend the investigation of energy metabolism during MFD. Voluntary intake decreased (P < 0.001) by 1.5 kg/d during CLA-induced MFD in the 14 studies analyzed, but the reduction in intake only partially accounts for the energy spared from reduced milk fat synthesis. Results are consistent with energy spared from the reduction in milk fat synthesis being partitioned toward adipose tissue fat stores during short-term MFD.
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PMID:Expression of enzymes and key regulators of lipid synthesis is upregulated in adipose tissue during CLA-induced milk fat depression in dairy cows. 1921 29

Plant oils in the diet are known to alter milk fat composition owing to changes in the supply of fatty acid precursors and/or activity of lipogenic enzymes in the mammary gland. Thirteen mid-lactating Alpine goats were used in a 3 x 3 Latin square design with 28-d periods to evaluate possible mechanisms regulating milk fat synthesis and fatty acid composition on grass hay-based diets containing none (H) or 55 g/kg diet dry matter of sunflower-seed oil (HSO) or linseed oil (HLO). Inclusion of oils in the diet had no effect on milk yield but enhanced (P<0.05) milk fat secretion. Compared with the control, HLO and HSO decreased (P<0.05) C10-C16 secretion and increased (P<0.05) C18 output in milk, responses that were accompanied by reductions in milk fat cis-9 14:1/14:0, cis-9 18:1/18:0 and cis-9, trans-11 18:2/cis-9 18:1 concentration ratios. Plant oil supplements decreased (P<0.05) mammary stearoyl-CoA desaturase (SCD) activity but had no effect on SCD mRNA. Treatments had no effect on glucose-6-phosphate dehydrogenase, malic enzyme and glycerol-3-phosphate dehydrogenase activity, or mRNA abundance and/or activity of lipoprotein lipase, acetyl-CoA carboxylase and fatty acid synthase in mammary, hepatic or adipose tissue. The results provided little support for milk fatty acid secretion responses to HLO and HSO being mediated via changes in mammary, hepatic or adipose mRNA abundance or in the activity of key lipogenic enzymes. In conclusion, plant oils in the diet enhance milk fat synthesis, alter milk fatty acid composition and specifically inhibit mammary SCD activity in the goat. Furthermore, the results suggest that the regulation of mammary lipogenesis in response to plant oils appears related to factors other than altered mammary gene expression or potential lipogenic enzyme activity.
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PMID:Effect of sunflower-seed oil or linseed oil on milk fatty acid secretion and lipogenic gene expression in goats fed hay-based diets. 1928 29


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