Genes in the sterol regulatory element-binding protein-1 (SREBP1) pathway play a central role in regulation of milk fat synthesis, especially the de-novo synthesis of saturated fatty acids. SCD, a SREBP-responsive gene, is the key enzyme in the synthesis of monounsaturated fatty acids in the mammary gland. In the present study, we discovered SNP in candidate genes associated with this signallin...

Obesity is associated with higher incidence of cancer, but the predisposing mechanisms remain poorly understood. The NAD(+)-dependent deacetylase SirT1 orchestrates metabolism, cellular survival, and growth. However, there is no unifying mechanism to explain the metabolic and tumor-related effects of SirT1. In this work, we demonstrate that genetic ablation of the endogenous inhibitor of SirT1,...

As part of a shift toward macromolecule production to support continuous cell proliferation, cancer cells coordinate the activation of lipid biosynthesis and the signaling networks that stimulate this process. A ubiquitous metabolic event in cancer is the constitutive activation of the fatty acid biosynthetic pathway, which produces saturated fatty acids (SFAs) and monounsaturated fatty acids (...

Uromodulin-associated kidney disease (UAKD) is a hereditary progressive renal disease which can lead to renal failure and requires renal replacement therapy. UAKD belongs to the endoplasmic reticulum storage diseases due to maturation defect of mutant uromodulin and its retention in the enlarged endoplasmic reticulum in the cells of the thick ascending limb of Henle's loop (TALH). Dysfunction o...

Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition of excess triglycerides within liver cells, a hallmark of NAFLD, is associated with a loss of insulin sensitivity, it is not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate...

Obesity and its metabolic complications are associated with increased expression/activity of stearoyl-CoA desaturase-1 (SCD1), a major regulator of lipid metabolism. Reduction or ablation of this enzyme is associated with an improved metabolic profile and has gained attention as a target for pharmaceutical development. Sterculic oil (SO) is a known inhibitor of SCD1 and may provide a natural ap...

There are four known stearoyl-CoA desaturase (SCD) enzyme isoforms in mouse and two in humans that are required for the biosynthesis of monounsaturated fatty acids, mainly oleate. SCD1 isoform plays a role in the regulation of energy metabolism and lipid synthesis, but the roles of the other SCD isoforms have not been investigated. Here we show that the SCD2 isoform is important in lipid synthe...

The development and maintenance of defining features of cancer, such as unremitting cell proliferation, evasion of programmed cell death, and the capacity for colonizing local tissues and distant organs, demand a massive production of structural, signaling and energy-storing lipid biomolecules of appropriate fatty acid composition. Due to constitutive activation of fatty acid biosynthesis, canc...

Macroautophagy, a major degradation pathway of cytoplasmic components, is carried out through formation of a double-membrane structure, the autophagosome. Although the involvement of specific lipid species in the formation process remains largely obscure, we recently showed that mono-unsaturated fatty acids (MUFA) generated by stearoyl-CoA desaturase 1 (SCD1) are required for autophagosome form...

The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion...