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J Clin Invest. 2012 Jan;122(1):142-52. doi: 10.1172/JCI43134. Epub 2011 Dec 27.

Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice.

Author information

1
Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes, and Metabolism, Center for Life Sciences, Boston, Massachusetts, USA.

Abstract

In the CNS, the hypothalamic arcuate nucleus (ARN) energy-balance circuit plays a key role in regulating body weight. Recent studies have shown that neurogenesis occurs in the adult hypothalamus, revealing that the ARN energy-balance circuit is more plastic than originally believed. Changes in diet result in altered gene expression and neuronal activity in the ARN, some of which may reflect hypothalamic plasticity. To explore this possibility, we examined the turnover of hypothalamic neurons in mice with obesity secondary to either high-fat diet (HFD) consumption or leptin deficiency. We found substantial turnover of neurons in the ARN that resulted in ongoing cellular remodeling. Feeding mice HFD suppressed neurogenesis, as demonstrated by the observation that these mice both generated fewer new neurons and retained more old neurons. This suppression of neuronal turnover was associated with increased apoptosis of newborn neurons. Leptin-deficient mice also generated fewer new neurons, an observation that was explained in part by a loss of hypothalamic neural stem cells. These data demonstrate that there is substantial postnatal turnover of the arcuate neuronal circuitry in the mouse and reveal the unexpected capacity of diet and leptin deficiency to inhibit this neuronal remodeling. This insight has important implications for our understanding of nutritional regulation of energy balance and brain function.

PMID:
22201680
PMCID:
PMC3248278
DOI:
10.1172/JCI43134
[Indexed for MEDLINE]
Free PMC Article

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