Hormonal
Dietary protein dilution (reducing protein to 5% of calories) improves glucose homeostasis and insulin sensitivity in both lean and obese models by inducing liver-derived FGF21 via the NUPR1 stress response, independent of UCP1 or total caloric intake.
This research suggests that significantly lowering dietary protein (to ~5% of calories) while keeping total calories constant can trigger a liver stress response (NUPR1/FGF21) that improves insulin sensitivity and glucose control, even in obesity. This works independently of weight loss. However, this is a complex metabolic manipulation observed in mice; it does not mean you should simply stop eating protein, as essential amino acids are required for basic function. The key finding is the *ratio* of protein to other macros, not just protein quantity.
In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21)... Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion...
Why this rating
Strong mechanistic evidence in mice (knockouts, liver-specific shRNA) and some human observational data, but lacks long-term human intervention trials.
Source
A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution
Adriano Maida et al. · Journal of Clinical Investigation · 2016
DOI 10.1172/jci85946
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