Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice

Yingga Wu; Baoguo Li; Li Li; Sharon E. Mitchell; Cara L. Green; Giuseppe D'Agostino; Guanlin Wang; Lu Wang; Min Li; Jianbo Li; Chaoqun Niu; Zengguang Jin; Anyongqi Wang; Yu Zheng; Alex Douglas; John R. Speakman

doi:10.1016/j.cmet.2021.01.017

Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice

Yingga Wu
, Baoguo Li
, Li Li
, Sharon E. Mitchell
, Cara L. Green
, Giuseppe D'Agostino
, Guanlin Wang
, Lu Wang
, Min Li
, Jianbo Li
, Chaoqun Niu
, Zengguang Jin
, Anyongqi Wang
, Yu Zheng
, Alex Douglas
, John R. Speakman

Chinese Academy of Sciences
University of the Chinese Academy of Sciences
University of Aberdeen
Institute of Biological and Environmental Sciences
University of Dali
Shenzhen Institutes of Advanced Technology

Research output: Contribution to journal › Article › peer-review

58 Citations (SciVal)

Abstract

The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.

Original language	English
Pages (from-to)	1264-1266
Number of pages	3
Journal	Cell Metabolism
Volume	33
Issue number	5
Early online date	4 Mar 2021
DOIs	https://doi.org/10.1016/j.cmet.2021.01.017
Publication status	Published - 1 Jun 2021

Data Availability Statement

The accession number for the transcriptome data for Figures 5 and S4 reported in this paper is GEO: GSE158215. The metabolomics data for Figure S5 have been deposited to Mendeley Data, and relevant DOI is as follows: https://doi: 10.17632/h96dcs23rr.1.

Funding

The study was funded by the National Key R&D Program of China (2019YFA0801900), Chinese Academy of Sciences Strategic Program (XDB13030100), the National Natural Science Foundation of China (31570409), the 1000 Talents program, a PIFI professorial fellowship award, the KC Wong Foundation, and a Wolfson merit award to J.R.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

energy expenditure
energy intake
hunger
low protein
mTOR signaling
obesity

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

Access to Document

10.1016/j.cmet.2021.01.017

Cite this

Wu, Y., Li, B., Li, L., Mitchell, S. E., Green, C. L., D'Agostino, G., Wang, G., Wang, L., Li, M., Li, J., Niu, C., Jin, Z., Wang, A., Zheng, Y., Douglas, A., & Speakman, J. R. (2021). Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice. Cell Metabolism, 33(5), 1264-1266. https://doi.org/10.1016/j.cmet.2021.01.017

Wu, Y, Li, B, Li, L, Mitchell, SE, Green, CL, D'Agostino, G, Wang, G, Wang, L, Li, M, Li, J, Niu, C, Jin, Z, Wang, A, Zheng, Y, Douglas, A & Speakman, JR 2021, 'Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice', Cell Metabolism, vol. 33, no. 5, pp. 1264-1266. https://doi.org/10.1016/j.cmet.2021.01.017

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title = "Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice",

abstract = "The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1\% to 20\% protein combined with either 60\% or 20\% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60\% fat. Moreover, they did not show hyperphagia when returned to a 20\% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1\% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1\% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.",

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author = "Yingga Wu and Baoguo Li and Li Li and Mitchell, \{Sharon E.\} and Green, \{Cara L.\} and Giuseppe D'Agostino and Guanlin Wang and Lu Wang and Min Li and Jianbo Li and Chaoqun Niu and Zengguang Jin and Anyongqi Wang and Yu Zheng and Alex Douglas and Speakman, \{John R.\}",

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AU - Wu, Yingga

AU - Li, Baoguo

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AU - Mitchell, Sharon E.

AU - Green, Cara L.

AU - D'Agostino, Giuseppe

AU - Wang, Guanlin

AU - Wang, Lu

AU - Li, Min

AU - Li, Jianbo

AU - Niu, Chaoqun

AU - Jin, Zengguang

AU - Wang, Anyongqi

AU - Zheng, Yu

AU - Douglas, Alex

AU - Speakman, John R.

PY - 2021/6/1

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N2 - The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.

AB - The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.

KW - energy expenditure

KW - energy intake

KW - hunger

KW - low protein

KW - mTOR signaling

KW - obesity

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ER -

Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice

Abstract

Data Availability Statement

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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