Ghrelin receptor deletion in AgRP neurons mitigates diet-induced obesity by activating thermogenesis

UM > Institute of Chinese Medical Sciences

Status	已發表Published
	Ghrelin receptor deletion in AgRP neurons mitigates diet-induced obesity by activating thermogenesis
	Lin, L.; Wu, C.; Lee, J.; Xu, A.; Xu, Y.; Sun, Y.
	2017-04-08
Source Publication	Cold Spring Harbor-Asia Conference: Lipid metabolism and metabolic disorders
Abstract	Ghrelin is the only orexigenic hormone known to stimulate growth hormone release, enhance feeding and promote weight gain. Ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in hypothalamic agouti-related peptide (AgRP) neurons. We recently reported that deletion of GHS-R in all neurons is sufficient to protect mice from diet-induced obesity (DIO) and effectively attenuates insulin resistance through activating non-shivering thermogenesis and enhancing physical activity. To define the specific underlying neuro-circuits mediating these important metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f) to investigate the role of GHS-R in AgRP neurons. The results showed that GHS-R in AgRP neurons is required to mediate ghrelin’s pharmacological effects on GH secretion, feeding initiation, and long-term adiposity, but has no effects on body length and long-term total food intake. Deletion of GHS-R in AgRP neurons mitigated DIO and improved insulin sensitivity. Our data further revealed that high fat diet fed-AgRP-cre;Ghsrf/f mice had increased energy expenditure, which was likely due to increased non-shivering thermogenesis. Consistently, under DIO condition AgRP-cre;Ghsrf/f mice were more cold-resistant, and showed enhanced thermogenic activation in both brown and subcutaneous fat. Our data showed that GHS-R in AgRP neurons regulates thermogenesis to modulate whole body lipid metabolism and insulin sensitivity. Thus GHS-R in AgRP neurons likely contributes to the pathogenesis of DIO through regulation of thermogenesis-associated energy metabolism.
Keyword	ghrelin receptor AgRP obesity thermogenesis
Language	英語English
The Source to Article	PB_Publication
PUB ID	29017
Document Type	Conference paper
Collection	Institute of Chinese Medical Sciences
Corresponding Author	Lin, L.
Recommended Citation GB/T 7714	Lin, L.,Wu, C.,Lee, J.,et al. Ghrelin receptor deletion in AgRP neurons mitigates diet-induced obesity by activating thermogenesis[C], 2017.
APA	Lin, L.., Wu, C.., Lee, J.., Xu, A.., Xu, Y.., & Sun, Y. (2017). Ghrelin receptor deletion in AgRP neurons mitigates diet-induced obesity by activating thermogenesis. Cold Spring Harbor-Asia Conference: Lipid metabolism and metabolic disorders.

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