First published March 1, 2006 - More info
Null mutations of the proopiomelanocortin gene (Pomc–/–) cause obesity in humans and rodents, but the contributions of central versus pituitary POMC deficiency are not fully established. To elucidate these roles, we introduced a POMC transgene (Tg) that selectively restored peripheral melanocortin and corticosterone secretion in Pomc–/– mice. Rather than improving energy balance, the genetic replacement of pituitary POMC in Pomc–/–Tg+ mice aggravated their metabolic syndrome with increased caloric intake and feed efficiency, reduced oxygen consumption, increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance. Pair-feeding of Pomc–/–Tg+ mice to the daily intake of lean controls normalized their rate of weight gain but did not abolish obesity, indicating that hyperphagia is a major but not sole determinant of the phenotype. Replacement of corticosterone in the drinking water of Pomc–/– mice recapitulated the hyperphagia, excess weight gain and fat accumulation, and hyperleptinemia characteristic of genetically rescued Pomc–/–Tg+ mice. These data demonstrate that CNS POMC peptides play a critical role in energy homeostasis that is not substituted by peripheral POMC. Restoration of pituitary POMC expression to create a de facto neuronal POMC deficiency exacerbated the development of obesity, largely via glucocorticoid modulation of appetite, metabolism, and energy partitioning.
James L. Smart, Virginie Tolle, Malcolm J. Low
Original citation: J. Clin. Invest.116:495 –505 (2006). doi:10.1172/JCI25243
Citation for this corrigendum: J. Clin. Invest.116:842 (2006). doi:10.1172/JCI25243C1
In the original article, reference 64 was cited incorrectly. The corrected reference appears below.
Coll, A.P., et al. 2005. Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoids. Diabetes.54:2269-2276.
The authors regret this error.