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Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding

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Science  28 Jun 2019:
Vol. 364, Issue 6447, pp. 1271-1274
DOI: 10.1126/science.aax1184

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Brain changes after overeating

A brain region called the lateral hypothalamic area is an integral node in the neurocircuitry controlling feeding behavior. In a mouse model of obesity, Rossi et al. found that a distinct class of neurons within this region acts as a brake on feeding, suppressing food intake (see the Perspective by Borgland). These neurons were potently and uniquely modified by diet-induced obesity. Thus, discrete populations of lateral hypothalamic area neurons are fundamental regulators of feeding behavior that might be targeted to treat eating disorders.

Science, this issue p. 1271; see also p. 1233

Abstract

The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)—a highly conserved brain region that orchestrates feeding—in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.

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