The HPA axis modulates the CNS melanocortin control of liver triacylglyceride metabolism

PHYSIOLOGY & BEHAVIOR

卷:105

Article

Wiedmer, Petra²  Rath, Michaela²  Nogueiras, Ruben^3,4  Wirth, Eva K.⁵  Kirchner, Henriette⁶  Schweizer, Ulrich⁵  Jonas, Wenke²  Veyrat-Durebex, Christelle⁷  Rohner-Jeanrenaud, Francoise⁷  Schuermann, Annette²  Joost, Hans-Georg²  Tschoep, Matthias H.²  Perez-Tilve, Diego¹ 

[1] Univ Cincinnati, Metab Dis Inst, Coll Med Internal Med, Dept Internal Med, Cincinnati, OH 45220 USA

[2] German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany

[3] Univ Santiago de Compostela, Sch Med, Dept Physiol, Inst Invest Sanitaria IDIS, Santiago De Compostela, Spain

[4] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela, Spain

[5] Charite, Inst Expt Endocrinol, D-13353 Berlin, Germany

[6] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[7] Univ Geneva, Fac Med, Dept Internal Med, Lab Metab,Div Endocrinol Diabetol & Nutr, Geneva, Switzerland

关键词: Melanocortin receptor;    Obesity;    Adrenalectomy;    Thyroidectomy;    SHU9119;    MTII;   

DOI  :  10.1016/j.physbeh.2011.10.019

来源: Elsevier

【 摘 要 】

The central melanocortin system regulates lipid metabolism in peripheral tissues such as white adipose tissue. Alterations in the activity of sympathetic nerves connecting hypothalamic cells expressing melanocortin 3/4 receptors (MC3/4R) with white adipocytes have been shown to partly mediate these effects. Interestingly, hypothalamic neurons producing corticotropin-releasing hormone and thyrotropin-releasing hormone co-express MC4R. Therefore we hypothesized that regulation of hypothalamo-pituitary adrenal (HPA) and hypothalamo-pituitary thyroid (HPT) axes activity by the central melanocortin system could contribute to its control of peripheral lipid metabolism. To test this hypothesis, we chronically infused rats intracerebro-ventricularly (i.c.v.) either with an MC3/4R antagonist (SHU9119), an MC3/4R agonist (MTII) or saline. Rats had been previously adrenalectomized (ADX) and supplemented daily with 1 mg/kg corticosterone (s.c.), thyroidectomized (TDX) and supplemented daily with 10 mu g/kg L-thyroxin (s.c.), or sham operated (SO). Blockade of MC3/4R signaling with SHU9119 increased food intake and body mass, irrespective of gland surgery. The increase in body mass was accompanied by higher epididymal white adipose tissue (eWAT) weight and higher mRNA content of lipogenic enzymes in eWAT. SHU9119 infusion increased triglyceride content in the liver of SO and TDX rats, but not in those of ADX rats. Concomitantly, mRNA expression of lipogenic enzymes in liver was increased in SO and TDX, but not in ADX rats. We conclude that the HPA and HPT axes do not play an essential role in mediating central melanocortinergic effects on white adipose tissue and liver lipid metabolism. However, while basal hepatic lipid metabolism does not depend on a functional HPA axis, the induction of hepatic lipogenesis due to central melanocortin system blockade does require a functional HPA axis. (C) 2011 Elsevier Inc. All rights reserved.

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