Journal
NEUROENDOCRINOLOGY
Volume 112, Issue 3, Pages 287-297Publisher
KARGER
DOI: 10.1159/000516834
Keywords
Agouti-related protein; Pro-opiomelanocortin; Leptin; Calorie-restriction; Obesity
Categories
Funding
- National Institutes of Health [R21-MH120614, R01-MH123545]
- University of Cincinnati College of Medicine [F102150]
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The study found that chronic calorie restriction or in db/db mice may alter the co-expression levels of Agrp and Pomc in POMC and AGRP neurons, suggesting an additional mechanism to further suppress melanocortin signaling under conditions of severely reduced leptin action.
Objectives: The control of energy balance relies on the counterbalancing release of neuropeptides encoded by the pro-opiomelanocortin (Pomc) and agouti-related protein (Agrp) genes, expressed by 2 distinct neuronal populations of the arcuate (ARC) nucleus of the hypothalamus. Although largely segregated, single-cell resolution techniques demonstrate some degree of co-expression. We studied whether challenges to the control of energy balance influence the degree of Agrp and Pomc co-expression in ARC melanocortin neurons. Methods: We used fluorescence-activated cell sorting followed by quantitative polymerase chain reaction and fluorescent in situ hybridization to measure Pomc and Agrp gene co-expression in POMC or AGRP neurons in response to (1) acute or chronic calorie restriction, or (2) obesity due to loss of leptin receptor expression or chronic high-fat diet feeding in male mice. Results: Melanocortin ARC neurons of fed mice exhibited low, yet detectable, levels of Pomc and Agrp gene co-expression. Calorie restriction significantly increased and decreased total Agrp and Pomc expression, respectively, and reduced the expression of Pomc relative to Agrp in AGRP neurons. Leptin-deficient db/db mice showed increased total Agrp levels and decreased Pomc expression, as well as significantly increased Agrp expression relative to Pomc in POMC neurons. Expression or co-expression levels did not differ between diet-induced obese mice and lean controls. Conclusions: Changes in Agrp and Pomc co-expression within POMC and AGRP neurons following chronic calorie restriction or in db/db mice suggest an additional mechanism to further suppress the melanocortin signaling during conditions of severely reduced leptin action.
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