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Pro‐opiomelanocortin gene delivery into the nucleus tractus solitarius ameliorates obesity and is characterized by unabated anorexia
Author(s) -
Li Gang,
Zhang Yi,
Chen KitYan,
Scarpace Philip J.
Publication year - 2006
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.20.5.a830-b
Subject(s) - medicine , endocrinology , melanocortin , hypothalamus , melanocortin 4 receptor , solitary nucleus , brainstem , neuropeptide , chemistry , receptor , biology
The role of the brainstem melanocortin (MC) system in the regulation of energy balance is not well defined. We activated the MC system in the nucleus tractus solitarius (NTS) of aged obese rats by recombinant adeno‐associated virus encoding pro‐opiomelanocortin (POMC) (rAAV‐POMC) or control vector delivered bilaterally into the NTS. There were sustained reductions in food intake and body weight in rAAV‐POMC compared with control over 42 days. At sacrifice, in rAAV‐POMC compared with control: NTS POMC expression increased 6‐fold; visceral adiposity decreased by 37%; tissue triglyeride contents diminished by 35% and 47% for liver and muscle, respectively, muscle fat oxidation increased as indicated by elevated acetyl‐CoA carboxylase phosphorylation, and there was improved insulin sensitivity. Hypothalamic MC3 receptor expression was reduced by 60% while neuropeptide Y, agouti‐related protein and MC4 receptor mRNA levels were unchanged in rAAV‐POMC rats. Whole body energy expenditure, assessed by indirect calorimetry, was not enhanced following POMC gene delivery, suggesting that the unabated hypophagia, unique to POMC overexpression in NTS, likely underlies these improvements. These data suggest long‐term activation of brainstem MC system may be more efficacious than comparable activation in hypothalamus. VA Medial Research and NIH, AG20985.