Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine

FGF21 is a potent metabolic regulator of energy balance, body composition, lipid metabolism, and glucose homeostasis. Initial studies reported that it was increased by fasting and the associated increase in ketones, but more recent work points to the importance of dietary protein and sensing of esse...

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Autores principales:	Han Fang, Kirsten P. Stone, Laura A. Forney, Desiree Wanders, Thomas W. Gettys
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	methionine restriction protein restriction energy expenditure essential amino acids (EAA) nutrient sensing mechanisms Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/b4b1dab8185642aa86d153dd13313a7e
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spelling	oai:doaj.org-article:b4b1dab8185642aa86d153dd13313a7e2021-12-01T18:09:42ZNutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine1664-239210.3389/fendo.2021.773975https://doaj.org/article/b4b1dab8185642aa86d153dd13313a7e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.773975/fullhttps://doaj.org/toc/1664-2392FGF21 is a potent metabolic regulator of energy balance, body composition, lipid metabolism, and glucose homeostasis. Initial studies reported that it was increased by fasting and the associated increase in ketones, but more recent work points to the importance of dietary protein and sensing of essential amino acids in FGF21 regulation. For example, dietary restriction of methionine produces a rapid transcriptional activation of hepatic FGF21 that results in a persistent 5- to 10-fold increase in serum FGF21. Although FGF21 is a component of a complex transcriptional program activated by methionine restriction (MR), loss-of-function studies show that FGF21 is an essential mediator of the resulting effects of the MR diet on energy balance, remodeling of adipose tissue, and enhancement of insulin sensitivity. These studies also show that FGF21 signaling in the brain is required for the MR diet-induced increase in energy expenditure (EE) and reduction of adiposity. Collectively, the evidence supports the view that the liver functions as a sentinel to detect and respond to changes in dietary amino acid composition, and that the resulting mobilization of hepatic FGF21 is a key element of the homeostatic response. These findings raise the interesting possibility that therapeutic diets could be developed that produce sustained, biologically effective increases in FGF21 by nutritionally modulating its transcription and release.Han FangKirsten P. StoneLaura A. ForneyDesiree WandersThomas W. GettysFrontiers Media S.A.articlemethionine restrictionprotein restrictionenergy expenditureessential amino acids (EAA)nutrient sensing mechanismsDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	methionine restriction protein restriction energy expenditure essential amino acids (EAA) nutrient sensing mechanisms Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	methionine restriction protein restriction energy expenditure essential amino acids (EAA) nutrient sensing mechanisms Diseases of the endocrine glands. Clinical endocrinology RC648-665 Han Fang Kirsten P. Stone Laura A. Forney Desiree Wanders Thomas W. Gettys Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
description	FGF21 is a potent metabolic regulator of energy balance, body composition, lipid metabolism, and glucose homeostasis. Initial studies reported that it was increased by fasting and the associated increase in ketones, but more recent work points to the importance of dietary protein and sensing of essential amino acids in FGF21 regulation. For example, dietary restriction of methionine produces a rapid transcriptional activation of hepatic FGF21 that results in a persistent 5- to 10-fold increase in serum FGF21. Although FGF21 is a component of a complex transcriptional program activated by methionine restriction (MR), loss-of-function studies show that FGF21 is an essential mediator of the resulting effects of the MR diet on energy balance, remodeling of adipose tissue, and enhancement of insulin sensitivity. These studies also show that FGF21 signaling in the brain is required for the MR diet-induced increase in energy expenditure (EE) and reduction of adiposity. Collectively, the evidence supports the view that the liver functions as a sentinel to detect and respond to changes in dietary amino acid composition, and that the resulting mobilization of hepatic FGF21 is a key element of the homeostatic response. These findings raise the interesting possibility that therapeutic diets could be developed that produce sustained, biologically effective increases in FGF21 by nutritionally modulating its transcription and release.
format	article
author	Han Fang Kirsten P. Stone Laura A. Forney Desiree Wanders Thomas W. Gettys
author_facet	Han Fang Kirsten P. Stone Laura A. Forney Desiree Wanders Thomas W. Gettys
author_sort	Han Fang
title	Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
title_short	Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
title_full	Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
title_fullStr	Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
title_full_unstemmed	Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
title_sort	nutritional regulation of hepatic fgf21 by dietary restriction of methionine
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b4b1dab8185642aa86d153dd13313a7e
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Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine

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