mTOR Signaling in X/A-Like Cells Contributes to Lipid Homeostasis in Mice

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Ziru LiWeizhen Zhang

Abstract

Gastric mechanistic target of rapamycin (mTOR) signaling is inversely associated with the expression and secretion of ghrelin, a 28-aa peptide hormone produced by gastric X/A-like cells. Ghrelin contributes to obesity and hepatic steatosis. We sought to control global lipid metabolism via the manipulation of gastric mTOR signaling in X/A-like cells. We established a ghrl-cre transgene in which the Cre enzyme is expressed in X/A-like cells under the control of the ghrelin-promoter. mTORflox/flox and tuberous sclerosis 1 (TSC1)flox/flox mice were separately bred with ghrl-cre mice to generate mTOR-ghrl-cre or TSC1-ghrl-cre mice, within which mTOR signaling was suppressed or activated, respectively. Lipid metabolism in liver and adipose depots was analyzed. Under the control of the ghrelin-promoter, the Cre enzyme was exclusively expressed in stomach X/A-like cells in adult animals. Knockout of mTOR in X/A-like cells increased circulating acyl-ghrelin and promoted hepatic lipogenesis with effects on adipose depots. Activation of mTOR signaling by deletion of its upstream inhibitor, TSC1, decreased ghrelin expression and secretion, altering lipid metabolism as evidenced by resistance to high-fat diet-induced obesity and hepatic ste...Continue Reading

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Citations

Aug 14, 2020·International Journal of Molecular Sciences·Veronica Pena-LeonLuisa Maria Seoane
Jun 23, 2020·International Journal of Endocrinology·Yonas AkaluBirhanu Ayelign

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