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Adrenocorticotropin Infusion Stimulates Glucocorticoid‐Receptor Mediated Lipolysis in Northern Elephant Seal Pups.
Author(s) -
Juarez Pablo,
VasquezMedina Jose Pablo,
Lee Debby,
Croker Daniel E.,
Ortiz Rudy M.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.889.5
Subject(s) - lipolysis , glucocorticoid , glucocorticoid receptor , endocrinology , medicine , seal (emblem) , biology , geography , adipose tissue , archaeology
Northern elephant seals (NES) experience a prolonged 2–3 month fasting period and rely primarily on the oxidation of fatty acids to meet their energetic needs. This fast is characterized by an increase in cortisol and non‐esterified fatty acids (NEFA's) leading to a lipid‐based metabolism (RQ=0.71). However, the functional relevance of this increase in cortisol and its influence on the glucocorticoid receptor (GR) in NES is not defined. We hypothesized that ACTH infusion increases lipolysis in NES. The contributions of cortisol and the GR were assessed by exogenous infusions of ACTH and/or concurrent blockade of the GR in the following groups: 1) Control, 2) ACTH (40 ACTH gel units), 3) GR‐blocker (400mg mifepristone in time‐release pellets) and 4) ACTH+GR‐blocker. Plasma, adipose and muscle biopsy samples 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) in the ACTH‐infused group suggesting glucocorticoids contribute to increased lipolysis. Mean adipose heat shock protein 90 (HSP90) levels increased 119% in the ACTH infused group and 192% in the ACTH+GR‐Blocker group suggesting that mifepristone has no residual effect on the binding of HSP90 to the glucocorticoid receptor, making this interaction imperative in GR‐mediated lipolysis. Lastly, mean muscle CD36 concentration increased 40% in the ACTH‐infused group suggesting that CD36 could contribute to the reduced intake of NEFA's. Collectively, this data suggests that the fasting‐associated increase in cortisol is an important contributing factor in stimulating lipolysis through the glucocorticoid receptor.Heat Shock Protein 90. Meanpercent change of HSP 90 in adipose tissue six days after treatment (T6). Asterisks denote significant (P<0.05) differences from pre‐treatment (T0).Plasma non‐esterified fatty acids (NEFA). Mean percent change from pre‐treatment of plasma NEFA after six days of treatment (T6). Asterisks denote significant (P<0.05 differences from pre‐treatment T0).Muscle tissue fatty acid translocate (CD36). Mean percent change of muscle tissue CD36 after six days of treatment (T6). Asterisks denote significant (P<0.05) differences from pre‐treatment (T0).