Despite advances in our understanding of the ways in which nutrient oversupply and triacylglycerol (TAG) anabolism contribute to hepatic steatosis, little is known about the lipases responsible for regulating hepatic TAG turnover. Recent studies have identified adipose triglyceride lipase (ATGL) as a major lipase in adipose tissue, although its role in the liver is largely unknown. Thus, we tested the contribution of ATGL to hepatic lipid metabolism and signaling. Adenovirus-mediated knockdown of hepatic ATGL resulted in steatosis in mice and decreased hydrolysis of TAG in primary hepatocyte cultures and
in vitro
assays. In addition to altering TAG hydrolysis, ATGL was shown to play a significant role in partitioning hydrolyzed fatty acids between metabolic pathways. Although ATGL gain and loss of function did not alter hepatic TAG secretion, fatty acid oxidation was increased by ATGL overexpression and decreased by ATGL knockdown. The effects on fatty acid oxidation coincided with decreased expression of peroxisome proliferator-activated receptor α (PPAR-α) and its target genes in mice with suppressed hepatic ATGL expression. However, PPAR-α agonism was unable to normalize the effects of ATGL knockdown on PPAR-α target gene expression, and this suggests that ATGL influences PPAR-α activity independently of ligand-induced activation. Conclusion: Taken together, these data show that ATGL is a major hepatic TAG lipase that plays an integral role in fatty acid partitioning and signaling to control energy metabolism. (Hepatology 2011)
11 January 2013 in Biological Trace Element Research
Previous studies have separately reported the contributions of dietary factors to the risk of cardiovascular disease (CVD) and its markers, including blood pressure (BP) and lipid profile. This study systematically reviewed the current evidence on this issue in the Korean population. Sixty-two studies from PubMed and Embase were included in this meta-analysis. We performed a random-effects model to analyze pooled odds ratios (ORs) and hazard ratios (HRs) and their 95% confidence intervals (CIs) for the consumption of 14 food items, three macro- and eight micro-nutrients, two dietary patterns, and three dietary indices. An analysis of pooled effect sizes from at least four individual study populations showed significant associations between coffee consumption and CVD (OR/HR, 0.71; 95% CI, 0.52–0.97) and elevated/high triglycerides (TG) (OR, 0.84; 95% CI, 0.78–0.90), sugar-sweetened beverage intake and elevated BP (OR/HR, 1.20; 95% CI, 1.09–1.33), and milk and dairy intake and elevated/high TG and low high-density lipoprotein cholesterol (HDL-C) (OR/HR, 0.82; 95% CI, 0.76–0.89 for both). Carbohydrate consumption and the low-carbohydrate-diet score were consistently related to an approximately 25% risk reduction for elevated TG and low HDL-C. A lower risk of elevated total cholesterol, but not low-density lipoprotein, was additionally observed for those with a higher low-carbohydrate-diet score. A healthy dietary pattern was only associated with a reduced risk of elevated TG in the Korea National Cancer Screenee Cohort (OR, 0.81; 95% CI, 0.67–0.98). This study showed that milk and dairy and coffee had protective effects for CVD and its risk factors, such as BP and lipid profile, while sugar-sweetened beverages exerted harmful effects.