Journal
ENDOCRINOLOGY
Volume 154, Issue 1, Pages 172-183Publisher
ENDOCRINE SOC
DOI: 10.1210/en.2012-1643
Keywords
-
Categories
Funding
- National Institutes of Health (NIH)
- National Institutes of Diabetes and Digestive and Kidney Diseases [R01DK080427]
- Weston Havens Foundation
- National Institute of General Medical Science [5K12GM081266-02]
- NIH-National Institutes of Diabetes and Digestive and Kidney Diseases [R01 DK58148, 5R01DK085916-02]
- NIH Diabetes and Endocrinology Research Center [P30 DK063720]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK080427, R01DK085916, P30DK063720, R01DK058148] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [K12GM081266] Funding Source: NIH RePORTER
Ask authors/readers for more resources
In many mammals, body weight increases continuously throughout adulthood until late middle age. The hormone leptin is necessary for maintaining body weight, in that high levels of leptin promote negative energy balance. As animals age, however, their increase in body weight is accompanied by a steady rise in circulating leptin levels, indicating the progressive development of counterregulatory mechanisms to antagonize leptin's anorexigenic effects. Hypothalamic neurons coexpressing agouti-related peptide (AgRP) and neuropeptide Y are direct leptin targets. These neurons promote positive energy balance, and they inhibit anorexigenic proopiomelanocortin (POMC) neurons via direct neuropeptide action and release of gamma-aminobutyric acid. We show here that AgRP and neuropeptide Y innvervation onto POMC neurons increases dramatically with age in male mice. This is associated with progressive increase of inhibitory postsynaptic currents and decrease of POMC firing rate with age. Neuronal activity is significantly attenuated in POMC neurons that receive a high density of AgRP puncta. These high-density AgRP inputs correlate with leptin levels in normal mice and are nearly absent in mice lacking leptin. The progression of increased AgRP innervation onto POMC somas is accelerated in hyperleptinemic, diet-induced obese mice. Together our study suggests that modulation of hypothalamic AgRP innervation constitutes one mechanism to counter the effects of the age-associated rise in leptin levels, thus sustaining body weight and fat mass at an elevated level in adulthood. (Endocrinology 154: 172-183, 2013)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available