Low Protein Diet Fat Loss

Highlights

• •

  Very low protein caused decreased body fat and improved glucose tolerance

• •

  Fatty acid and amino acid metabolism were changed by dietary low protein

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  The 1% protein group did not show hyperphagia despite the hunger pathway being activated

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  The effect of 1% protein on food intake was linked to hypothalamic mTOR signaling

Summary

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.

Graphical abstract

Keywords

• obesity
• low protein
• energy intake
• energy expenditure
• hunger
• mTOR signaling

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Article Info

Publication History

Published: March 4, 2021

Accepted: January 21, 2021

Received in revised form: October 5, 2020

Received: March 13, 2020

Identification

DOI: https://doi.org/10.1016/j.cmet.2021.01.017

Copyright

© 2021 Published by Elsevier Inc.

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Low Protein Diet Fat Loss

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