Effects of dehydroepiandrosterone on fatty acid profiles in Zucker rats: Evidence for decreasing insulin resistanc

Elevated serum free fatty acids (FFA) levels and altered tissue fatty acid (FA) profiles may be two important metabolic changes in obesity leading to insulin resistance (IR) and type 2 diabetes mellitus (DM). Dehydroepiandrosterone (DHEA), the most abundant human adrenal steroid, decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth onset obesity, IR, and type 2 DM. This study was conducted to: (1) determine if serum FFA levels in lean and obese ZRs correlate with serum and tissue metabolic parameters of altered energy metabolism and IR, and to (2) investigate DHEA's effects on lean and obese ZR serum FFA levels and tissue FA profiles.;It is hypothesized that (1) serum FFA levels would be a predictor of serum and tissue metabolic parameters that govern IR, and that (2) DHEA would alter serum FFA levels and tissue FA profiles of the obese ZR so that they closer resemble the levels and profiles of the lean. Perhaps DHEA alters specific serum and/or tissue lipid FAs to regulate their flux and lower IR.;The results of this work show that serum FFA levels are higher in obese (∼1 mmol/L) compared to lean (∼0.6 mmol/L) ZRs. Furthermore, 30 but not 7 days of consuming a 50% fat diet supplemented with 0.6% DHEA significantly (p ≤ 0.05) decreased serum FFA levels in both lean and obese ZRs. Strong correlations exist between serum FFA levels and metabolic parameters related to IR when considering values from both lean and obese ZRs.;FA profiles from several insulin sensitive tissue were different in obese compared to lean ZRs. Additionally, DHEA treatment altered specific muscle FA profiles in muscle that have been shown to predict IR. For example, the proportions of long chain polyunsaturated FAs, specifically, arachidonic acid (AA), is low in insulin resistant muscle. In this study, obese rats have lower proportions of AA compared to lean, and DHEA proportionally increases AA in the muscle of both obese and lean rats. This study proposes a mechanism by which IR could be lowered by such DHEA-induced FA profile alterations.