Liver X receptors (LXRs), including LXRalpha and LXRbeta, are intracellular sterol sensors that regulate expression of genes controlling fatty acid and cholesterol absorption, excretion, catabolism, and cellular efflux. Because the kidney plays an important role in lipid metabolism and dyslipidemia accelerates renal damage, we investigated the effect of TO-901317, an LXR agonist, on the gene ex...

OBJECTIVE TR4 is a nuclear receptor without clear pathophysiological roles. We investigated the roles of hepatic TR4 in the regulation of lipogenesis and insulin sensitivity in vivo and in vitro. RESEARCH DESIGN AND METHODS TR4 activity and phosphorylation assays were carried out using hepatocytes and various TR4 wild-type and mutant constructs. Liver tissues from TR4 knockout, C57BL/6, and d...

Worldwide obesity rates have risen to epidemic proportions, with over 600 million obese individuals across the globe. These individuals are prone to obesity-related health complications, including type 2 diabetes, hypertension, cancer, and cardiovascular disease. Obesity also coincides with the expansion of adipose tissue, which has an important role storing excess calories in the form of triac...

Stearoyl-CoA desaturase (SCD) is a microsomal enzyme required for the biosynthesis of oleate and palmitoleate, which are the major monounsaturated fatty acids of membrane phospholipids, triglycerides, and cholesterol esters. Two well characterized isoforms of SCD, SCD1 and SCD2, exist in the mouse. Most mouse tissues express SCD1 and 2 with the exception of the liver, which expresses mainly the...

Stearoyl-CoA desaturase 1 (SCD1) activity, a key regulator of lipid metabolism, may be associated with the development of metabolic syndrome (MetS). We examined the association of genetic variation in the SCD1 gene with the occurrence of MetS and its five components in a population of Costa Rican adults (n = 2152; mean age, 58 y; range, 18-86 y). Associations of tag single nucleotide polymorphi...

The peroxisomal 3-ketoacyl-CoA thiolase B (Thb) gene was previously identified as a direct target gene of PPARalpha, a nuclear hormone receptor activated by hypolipidemic fibrate drugs. To better understand the role of ThB in hepatic lipid metabolism in mice, Sv129 wild-type and Thb null mice were fed or not the selective PPARalpha agonist Wy14,643 (Wy). Here, it is shown that in contrast to so...

Primary cicatricial alopecias (PCAs) are heterogeneous disorders characterized by the replacement of hair follicle (HF) structures fibrous tissue, leading to permanent loss. The underlying pathogenesis and treatment options poorly due lack preclinical research models. asebia mouse, which harbors mutations in stearoyl-CoA desaturase 1 (Scd1) gene, was previously proposed as a model for PCA, howe...

Thiazolidinediones (TZDs) are known to have potent increases of insulin sensitivity. Because peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a receptor for TZDs, is mainly expressed in adipocytes, we tried to search the TZD-targeted genes in mouse 3T3-L1 adipocytes. By the mRNA differential display method, one band repressed by troglitazone was obtained, which corresponded to the...

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...

OBJECTIVE Increased plasma levels of free fatty acids occur in obesity and type 2 diabetes and contribute to the development of insulin resistance. Saturated fatty acids (SFAs) such as palmitate especially have lipotoxic effects leading to endoplasmatic reticulum (ER) stress, inflammation, and insulin resistance. Stearoyl-CoA desaturase 1 (SCD1) plays a key role in preventing lipotoxic effects,...