The human ADFP gene is a direct liver-X-receptor (LXR) target gene and differentially regulated by synthetic LXR ligands.

Expression of adipocyte differentiation-related protein (ADFP), residing on the surface of lipid droplets, correlates to hepatic fat storage. In the context of consequences and treatment of metabolic disorders, including hepatic steatosis, it is imperative to gain knowledge about the regulation of the human ADFP gene. The nuclear receptor liver-X-receptor (LXR) is a key regulator of hepatic fatty acid biosynthesis and cholesterol homeostasis as well as a potential drug target.

Ghrelin induces abdominal obesity via GHS-R-dependent lipid retention.

Circulating ghrelin elevates abdominal adiposity by a mechanism independent of its central orexigenic activity. In this study we tested the hypothesis that peripheral ghrelin induces a depot-specific increase in white adipose tissue (WAT) mass in vivo by GH secretagogue receptor (GHS-R(1a))-mediated lipolysis. Chronic iv infusion of acylated ghrelin increased retroperitoneal and inguinal WAT volume in rats without elevating superficial sc fat, food intake, or circulating lipids and glucose.

Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats.

Liver X receptors (LXRs), activated by oxysterols, play an important role in the regulation of lipid and glucose metabolism, which is also markedly dependent on thyroid hormone and growth hormone (GH) status. Here, we investigated how a 1-week exposure to the synthetic LXR agonist T0901317 affected GH secretion and thyroid hormone status in male rats. While the pulse frequency of GH secretion was marginally affected there was a highly significant decrease in the triiodo-L-thyronine/thyroxine (T3/T4) ratio in plasma.

Physiological differences between human and rat primary hepatocytes in response to liver X receptor activation by 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phenylacetic acid hydrochloride (GW3965).

The liver is central to the maintenance of glucose and lipid homeostasis, and liver X receptors (LXRs) are key regulators of expression of the genes involved. So far, effects of activation of LXR in human hepatocytes have not been well characterized. Here we show that treatment of primary human hepatocytes with the synthetic LXR ligand 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phenylacetic acid hydrochloride (GW3965) results in reduced output of bile acids and very low density lipoprotein triglycerides and induced expression of adipose differentiation-related protein accompanied by increased lipid storage.

Activation of the glucocorticoid receptor or liver X receptors interferes with growth hormone-induced akr1b7 gene expression in rat hepatocytes.

The akr1b7 gene encodes an aldo-keto reductase involved in detoxification of isocaproaldehyde, the product from side chain cleavage of cholesterol, and of 4-hydroxynonenal (4-HNE) formed by lipid peroxidation and cleavage. Here we show that the expression of akr1b7 mRNA in rat liver is sexually differentiated, expressed in females but not in males, and regulated by the sexually dimorphic secretion pattern of GH. A GH dose-dependent induction of akr1b7 was demonstrated in cultured primary rat hepatocytes, which was sensitive to cycloheximide.