Abstract
The pleiotropic hormone‐like polypeptide, fibroblast growth factor 21 (FGF21), is a major modulator of lipid and glucose metabolism and an exploratory treatment strategy for obesity related metabolic disorders. Recombinant FGF21 (rFGF21) is currently being investigated as therapeutic against high blood lipids and type‐2 diabetes. However, the high costs of producing rFGF21 and the mode of delivery by injection are important limitations to its wide therapeutic use. A cost effective and practical alternative is to stimulate endogenous FGF21 production through diet. Our research shows that naturally occurring dietary compound R‐α‐lipoic acid (LA) stimulates liver Fgf21 expression (+175%) and blood FGF21 levels (+330%) and replicates the adaptive metabolic response to fasting supported by FGF21 in vivo. In the present study, we interrogate FGF21 promoter regulation from HepG2 human hepatocellular carcinoma cells under fed and starved states and in the presence of LA. We employed Formaldehyde‐Assisted Isolation of Regulatory Elements (FAIRE)‐coupled qPCR to quantify nucleosome‐depleted regions in the promoter. Our results provide new insights into how nutrient‐responsive transcription factor binding sites regulate FGF21. The potential impact of this work is that LA may prove to be a safe and affordable means to stimulate FGF21 production.Grant Funding Source: Supported by UNL Faculty Seed Grant, and Layman Seed Award.
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