Intestinal stearoyl-CoA desaturase-1 regulates energy balance via alterations in bile acid homeostasis

Abstract

AbstractBackground and AimsStearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids into monounsaturated fatty acids and plays an important regulatory role in lipid metabolism. Previous studies have demonstrated that mice deficient in SCD1 are protected from diet-induced obesity and hepatic steatosis due to altered lipid esterification and increased energy expenditure. Previous studies in our lab have shown that intestinal SCD1 modulates intestinal and plasma lipids and alters cholesterol metabolism. Here we investigated a novel role for intestinal SCD1 in the regulation of systemic energy balance.MethodsTo interrogate the role of intestinal SCD1 in modulating whole body metabolism, intestine-specificScd1knockout (iKO) mice were maintained on standard chow diet or challenged with a high-fat diet (HFD). Studies included analyses of bile acid content and composition, metabolic phenotyping including body composition, indirect calorimetry, glucose tolerance analyses, and assessment of bile acid signaling pathways.ResultsiKO mice displayed elevated plasma and hepatic bile acid content and decreased fecal bile acid excretion, associated with increased expression of the ileal bile acid uptake transporter,Asbt. These increases were associated with increased expression of TGR5 targets, includingDio2in brown adipose tissue and elevated plasma glucagon-like peptide-1 levels. Upon HFD challenge, iKO mice had reduced metabolic efficiency apparent through decreased weight gain despite higher food intake. Concomitantly, energy expenditure was increased, and glucose tolerance was improved in HFD-fed iKO mice.ConclusionOur results indicate that deletion of intestinal SCD1 has significant impacts on bile acid metabolism and whole-body energy balance, likely via activation of TGR5.