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Review
. 2024 Jan 10;16(2):229.
doi: 10.3390/nu16020229.

Protein Restriction in Metabolic Health: Lessons from Rodent Models

Khuhee Na  1   2 , Yoon Jung Park  1   2
Affiliations
Review

Protein Restriction in Metabolic Health: Lessons from Rodent Models

Khuhee Na et al. Nutrients. .

Abstract

Consumption of protein-rich diets and supplements has been increasingly advocated by individuals seeking to optimize metabolic health and mitigate the effects of aging. Protein intake is postulated to support muscle mass retention and enhance longevity, underscoring its perceived benefits in age-related metabolic regulation. However, emerging evidence presents a paradox; while moderate protein consumption contributes to health maintenance, an excessive intake is associated with an elevated risk of chronic diseases, notably obesity and diabetes. Furthermore, recent studies suggest that reducing the ratio of protein intake to macronutrients improves metabolic parameters and extends lifespan. The aim of this study is to review the current evidence concerning the metabolic effects of protein-restricted diets and their potential mechanisms. Utilizing rodent models, investigations have revealed that protein-restricted diets exert a notable influence over food intake and energy consumption, ultimately leading to body weight loss, depending on the degree of dietary protein restriction. These phenotypic alterations are primarily mediated by the FGF21 signaling pathway, whose activation is likely regulated by ATF4 and the circadian clock. The evidence suggests that protein-restricted diets as an alternative approach to calorie-restricted regimes, particularly in overweight or obese adults. However, more research is needed to determine the optimal level of restriction, duration, and long-term effects of such interventions.

Keywords: FGF21; circadian clock; circadian rhythm; macronutrients; protein restriction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Changes in body weight, food (or energy) intake, and energy expenditure, depending on the level of dietary protein restriction in rodent studies. The trend of changes in body weight, food (or energy) intake, and energy expenditure according to the level of protein restriction compared to the control diet group is indicated by arrows and bars. Blue and red arrows indicate when the indicators decreased or increased in the protein-restricted group, respectively, and black bars indicate when there was no significant difference compared to the control diet group [2,22,27,28,29,30,31,32,34,35,36,37,38].
Figure 2
Figure 2
Potential mechanisms by which protein dilution alters body weight, food (or energy) intake, and energy expenditure. The arrow next to each word indicates an increase in activity.
Figure 3
Figure 3
Possible mechanisms of inducing the expression of Fgf21 in low-protein diet. Results with sufficient evidence are indicated by solid black arrows, while results with suggestive evidence are indicated by dashed black arrows. In addition, red arrows next to a transcriptional factor and FGF21 indicate an increase or decrease in its expression.
See this image and copyright information in PMC

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