title: The HPA axis modulates the CNS melanocortin control of liver triacylglyceride metabolism.
abstract: 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 intracerebroventricularly (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 1mg/kg corticosterone (s.c.), thyroidectomized (TDX) and supplemented daily with 10 μg/kgL-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.
authors: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors: Petra
authors: P
authors: Wiedmer
authors: Nilika
authors: N
authors: Chaudhary
authors: Michaela
authors: M
authors: Rath
authors: Chun-Xia
authors: CX
authors: Yi
authors: Gayathri
authors: G
authors: Ananthakrishnan
authors: Rubén
authors: R
authors: Nogueiras
authors: Eva K
authors: EK
authors: Wirth
authors: Henriette
authors: H
authors: Kirchner
authors: Ulrich
authors: U
authors: Schweizer
authors: Wenke
authors: W
authors: Jonas
authors: Christelle
authors: C
authors: Veyrat-Durebex
authors: Francoise
authors: F
authors: Rohner-Jeanrenaud
authors: Annette
authors: A
authors: Schürmann
authors: Hans-Georg
authors: HG
authors: Joost
authors: Matthias H
authors: MH
authors: Tschöp
authors: Diego
authors: D
authors: Perez-Tilve
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems; D004435:Eating / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008099:Liver / Q000378:metabolism*; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000819:agonists / Q000037:antagonists & inhibitors; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D053486:Melanocortins; D009479:Neuropeptides; D018043:Receptors, Corticotropin; D014280:Triglycerides; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; C099323:cortistatin; C103272:SHU 9119; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D013974:Thyroxine; D003345:Corticosterone