Uday Saxena
Tanzania
Research Article
Identification of a Pharmacological Inducer of Lipoic Acid Synthase that Impacts Mitochondrial Function: Metabolic Benefits and Body Weight Loss without Changes in Caloric Intake
Author(s): Indira Padmalayam, Rebecca Hamm, D. Srinivas Reddy, Debnath Bhuniya, Angela Vines, Sujatha Seenu, Ranjan Chakrabarti, Uday Saxena and Sivaram PillarisettiIndira Padmalayam, Rebecca Hamm, D. Srinivas Reddy, Debnath Bhuniya, Angela Vines, Sujatha Seenu, Ranjan Chakrabarti, Uday Saxena and Sivaram Pillarisetti
Objective: Lipoic Acid Synthase (LASY) was recently shown to play a critical role in inflammation, mitochondrial function and insulin resistance. In this study using a pharmacological inducer of LASY as a tool, we studied the effects of LASY induction in vivo in rodent models of obesity and type 2 diabetes.
Methods: We identified a small molecule that increases LASY mRNA and lipoic acid levels in vitro. Effect of the inducer (compound 1) on body weight, food intake, energy expenditure and metabolic parameters was studied in rodent models of genetic and diet-induced obesity.
Results: Compound 1 was identified as a transcriptional inducer of LASY. In vitro, compound 1 increased LASY mRNA expression, mitochondrial lipoic acid levels and improved mitochondrial function in cultured skeletal muscle cells. LASY mRNA and lipoic acid levels were significantly increased in skele.. View More»
