Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men.
Level 3 - non-randomized controlled study
Prospective human dietary intervention with mechanistic mouse model
PubMed 40050437 · doi:10.1038/s42255-025-01236-7
What was done
Lean, healthy men consumed a protein-restricted diet meeting minimum protein requirements for 5 weeks—with protein replaced by either carbohydrates or fats—followed by 5 weeks of reverting to their customary higher-protein diet. Investigators assessed the caloric intake required to maintain stable body weight, measured fasting plasma FGF21 concentrations, and conducted proteomic analysis of human white adipose tissue alongside validation in FGF21-knockout mice.
What was found
The abstract reports no numerical values, effect sizes, or p-values. It qualitatively states that maintaining body weight during protein restriction required an increase in energy intake regardless of whether protein was replaced with carbohydrates or fats. Energy requirements returned to baseline when returning to customary protein intake. Fasting plasma FGF21 levels increased during protein restriction, and adipose tissue proteomics revealed alterations in mitochondrial electron transport chain components that were FGF21-dependent in male mice.
Why it matters
This study provides human translational evidence that dietary protein restriction increases metabolic energy requirements via FGF21-related adipose adaptations, bridging prior rodent findings to human physiology.
Limits
The abstract omits sample size, participant demographics, and exact quantitative data. The study included only lean, healthy men, precluding generalization to females, older adults, or individuals with metabolic disease. The intervention duration was limited to 5 weeks.
Cited by
- supports A low-protein, high-sugar diet stimulates the generation of fibroblast growth factor (FGF), which converts into high metabolic energy.