AgRP neuronal ATF4 regulates energy metabolism
Abstract
The central nervous system, especially the hypothalamus, plays a key role in the regulation of energy balance. The arcuate nucleus (ARC) of the hypothalamus contains two major classes of neurons that regulate metabolism: one is appetite suppressor neurons, such as Poirogenin (POMC) neurons; One group is appetite promoting neurons, including neuropeptide Y (NPY) and AgRP gene related protein (AgRP) neurons. Using induced gene knockout technique, it was found that specific knockout activation of transcription factor 4 (ATF4) in AgRP neurons in adult mice resulted in decreased body weight and increased sensitivity to insulin and leptin. At the same time, the experimental mice eat less, the energy consumption increases, and the body heat production increases. Moreover, AgRP-specific knockout ATF4 mice could resist hyperlipid-induced obesity, insulin resistance and fatty liver. Further study of its mechanism of action showed that ATF4 could bind to the promoter of FOXO1 and directly regulate its expression. After injecting FOXO1 adenovirus into the arcuate nucleus of the hypothalamus, knockout mice showed significant fat gain. This study found that ATF4 plays an important role in regulating energy balance and lipid metabolism in hypothalamic AgRP neurons, suggesting that ATF4 may be a new drug target in the treatment of obesity and metabolic diseases. The work was published in Diabetes in 2017.
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