Adipose Tissue Fatty Acid Synthase Research Articles

Preliminary study on effect of Gegen Qinlian Decoction on enzyme activity, gene expression and methylation level of FASN in adipose tissue of rats with insulin resistance

To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.

Dietary betaine supplementation has energy-sparing effects in feedlot cattle during summer, particularly in those without access to shade

Dietary betaine supplementation improves water retention in steers and may influence lean-tissue deposition, while also acting as an osmolyte to help regulate cellular osmotic balance. This study investigated the interactions between shade and dietary betaine on carcass characteristics, tissue enzyme activity and gene expression in 48 feedlot steers during summer. Steers were randomly allocated to a 4 × 2 factorial design with the factors being dietary betaine (0, 10, 20 or 40 g) and shade (with and without shade) for 120 days. Tissue samples were obtained at slaughter and analysed for gene expression of heat shock proteins 70 and 90 (HSP70/90) and expression of heat shock factor 1 (HSF1), and enzyme activity of fatty acid synthase (FAS) and glycerol-6-phosphate dehydrogenase (G6PDH). Carcasses were evaluated for quality. Carcass weight at slaughter was not altered by shade (P = 0.18) but tended to be increased by dietary betaine (306 v. 314 kg, P = 0.09). The P8 backfat was not altered by shade (P = 0.43) or dietary betaine (P = 0.32), although there was a within dietary betaine effect whereby P8 backfat tended to be greater in steers fed 10 g compared with 40 g betaine/day (17.4 v. 14.5 mm, P = 0.06). Muscle pH at 1 h (5.97 v. 6.03, P = 0.01) and 2 h (5.73 v. 5.80, P = 0.04) post-slaughter was higher in shaded steers, and muscle pH at 1 h post-slaughter was higher in steers fed 10 or 20 g than those fed 40 g betaine/day (6.03 v. 6.03 v. 5.95, P = 0.005). Gene expression was not altered by betaine, while adipose tissues expressed more of each gene than muscle (P < 0.001). The mRNA expression of HSF1 and HSP90 was influenced by a shade × betaine interaction, although the direction of this interaction was irregular (P = 0.03 and 0.03, respectively). Adipose tissue FAS and G6PDH enzyme activity was unaffected by shade and betaine. The results of this study indicate that betaine supplementation may be a successful carcass modifier in growing feedlot steers during summer. Provision of shade during summer may reduce the rate of pH decline in the first 2 h after slaughter and reduce the risk of high rigor temperature.

Effect of rumen-protected choline supplementation on liver and adipose gene expression during the transition period in dairy cattle

We previously reported that supplementation of rumen-protected choline (RPC) reduces the hepatic triacylglycerol concentration in periparturient dairy cows during early lactation. Here, we investigated the effect of RPC on the transcript levels of lipid metabolism-related genes in liver and adipose tissue biopsies, taken at wk −3, 1, 3, and 6 after calving, to elucidate the mechanisms underlying this RPC-induced reduction of hepatic lipidosis. Sixteen multiparous cows were blocked into 8 pairs and randomly allocated to either 1 of 2 treatments, with or without RPC. Treatments were applied from 3wk before to 6wk after calving. Both groups received a basal diet and concentrate mixture. One group received RPC supplementation, resulting in an intake of 14.4g of choline per day, whereas controls received an isoenergetic mixture of palm oil and additional soybean meal. Liver and adipose tissue biopsies were taken at wk −3, 1, 3, and 6 to determine the mRNA abundance of 18 key genes involved in liver and adipose tissue lipid and energy metabolism. Milk samples were collected in wk 1, 2, 3, and 6 postpartum for analysis of milk fatty acid (FA) composition. The RPC-induced reduction in hepatic lipidosis could not be attributed to altered lipolysis in adipose tissue, as no treatment effect was observed on the expression of peroxisome proliferator-activated receptor γ, lipoprotein lipase, or FA synthase in adipose tissue, or on the milk FA composition. Rumen-protected choline supplementation increased the expression of FA transport protein 5 and carnitine transporter SLC22A5 in the liver, suggesting an increase in the capacity of FA uptake and intracellular transport, but no treatment effect was observed on carnitine palmitoyl transferase 1A, transporting long-chain FA into mitochondria. In the same organ, RPC appeared to promote apolipoprotein B-containing lipoprotein assembly, as shown by elevated microsomal triglyceride transfer protein expression and apolipoprotein B100 expression. Cows supplemented with RPC displayed elevated levels of glucose transporter 2 mRNA and a reduced peak in pyruvate carboxylase mRNA immediately after calving, showing that supplementation also resulted in improved carbohydrate metabolism. The results from this study suggest that RPC supplementation reduces liver triacylglycerol by improved FA processing and very-low-density lipoprotein synthesis, and RPC also benefits hepatic carbohydrate metabolism.

Enhanced glycerol 3-phosphate dehydrogenase activity in adipose tissue of obese humans.

The primary purpose of this investigation was to determine whether adipose tissue glycerol 3-phosphate dehydrogenase activity is associated with human obesity. The data presented in this paper indicate that the glycerol 3-phosphate dehydrogenase activity in adipose tissue from morbidly obese subjects is approximately 2-fold higher than from lean individuals. Moreover, positive correlation between adipose tissue glycerol 3-phosphate dehydrogenase activity and body mass index (BMI) (r = 0.5; p < 0.01) was found. In contrast, the adipose tissue fatty acid synthase (FAS) and ATP-citrate lyase (ACL) activities in morbidly obese patients are significantly lower than in lean subjects. Furthermore, negative correlation between adipose tissue FAS activity and BMI (r = -0.3; p < 0.05) as well as between ACL activity and BMI (r = -0.3; p < 0.05) was found. These data indicate that elevated glycerol 3-phosphate dehydrogenase might contribute to the increase of triacylglycerol (TAG) synthesis in obese subjects, however, fatty acids necessary for glycerol 3-phosphate esterification must be derived (because of lower FAS and ACL activities) mainly from TAG in circulating lipoproteins formed in liver (VLDL), and/or from the intake with food (chylomicrons). The conclusion is, that the enhanced activity of glycerol 3-phosphate dehydrogenase, and hence the generation of more glycerol 3-phosphate in adipose tissue offers a novel explanation for increased TAG production in adipose tissue of obese subjects.