Glucocorticoid‐Receptor Mediated Signaling Regulates Lipolysis in Northern Elephant Seal Pups

Abstract

Northern elephant seals (NES) experience prolonged 2–3 month fasting periods, relying primarily on the oxidation of fatty acids to meet their energetic needs (RQ=0.71). Although fasting periods are characterized by an increase in circulating cortisol (F) and non‐esterified fatty acids (NEFA's), the functional relevance such increase in cortisol in NES is not defined. We hypothesized that F lipolysis is regulated through glucocorticoid receptor signaling (GR) in NES. The contributions of F and the GR were assessed by exogenous infusions of ACTH and/or concurrent blockade of the GR in the following groups: (1) untreated control, (2) ACTH (80 units intramuscular injection (IM)) and (3) ACTH + GR blocker (RU486) (80 units IM + 400mg RU486 in time release pellets). Plasma, and adipose and muscle biopsies were collected at days 0 (T0; immediately prior to infusion) and 6 (T6). Mean plasma NEFA levels increased 38% (0.84 ± 0.13 vs 1.16 ± 0.06mM) from T0 to T6 with ACTH infusion suggesting glucocorticoids contribute to increased lipolysis. ACTH infusion increased mean adipose HSP90 expression by 92%±18.2 while decreasing mean muscle HSP90 expression by 39%±14.5 from T0 to T6 suggesting that HSP90 may participate in GR‐mediated lipolysis in adipose while contributing to conserving lipid sources in muscle. Mean muscle CD36 expression decreased 46%±12.2 from T0 to T6 with ACTH infusion suggesting that there is a reduced intake of NEFA's by skeletal muscle, contributing to increased circulating NEFAs during lipolysis. These data suggest that the fasting‐associated increase in GR signaling is imperative for sustaining elevated levels of lipolysis during the post weaning fast, and is dependent upon the functional role of cortisol and HSP90.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.