Dorsomedial hypothalamic NPY modulation of adiposity and thermogenesis

Abstract

In addition to controlling food intake, the dorsomedial hypothalamus (DMH) plays an important role in thermoregulation. Within the DMH, a number of neuropeptides and receptors have been found and their roles in controlling energy balance are being investigated. We recently found that the orexigenic neuropeptide Y (NPY) in the DMH has specific actions on body adiposity and thermogenesis using a viral-mediated manipulation of NPY in the DMH. Knockdown of NPY in the DMH promotes the development of brown adipocytes in white adipose tissue and increases brown adipocyte activity. DMH NPY knockdown also causes increased thermogenesis and energy expenditure. Finally, DMH NPY knockdown prevents high-fat diet-induced obesity and improves glucose homeostasis. This review focuses on the role of DMH NPY in modulating body adiposity and thermogenesis.

Keywords: Brown adipocyte development; Brown adipose tissue; Dorsomedial hypothalamus; Energy expenditure; Neuropeptide Y; Thermogenesis.

Figure 1

In situ hybridization with [³⁵S]-labeled antisense riboprobe of rodent or human Npy shows Npy gene expression in the arcuate nucleus (ARC) and/or the dorsomedial hypothalamus (DMH) in adult mouse (A), rat (B), and rhesus monkey brain (C).

Figure 2

Effects of DMH NPY knockdown on inguinal fat (A) and interscapular brown fat temperature (B) in rats receiving bilateral DMH injections of the vector adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) compared with the rats receiving bilateral DMH injections of the control vector containing scrambled shRNA (AAVshCTL). Rats were housed individually at room temperature condition (23±1°C) on a 12:12 hr light-dark cycle. Black bar indicates a dark period.