Hormonal
Genetic heterozygosity for the ER chaperone Grp78 (BiP) promotes an adaptive unfolded protein response (UPR) in white adipose tissue, which attenuates diet-induced obesity, insulin resistance, and hyperglycemia.
This research identifies a specific genetic mechanism (Grp78 heterozygosity) that protects against diet-induced obesity and insulin resistance by enhancing the cell's ability to handle stress (UPR). While this specific genetic modification is not a lifestyle intervention, it suggests that strategies which mildly activate adaptive stress responses (hormesis) in fat cells may improve metabolic health. Current research points to ER stress modulation as a potential therapeutic target for obesity and type 2 diabetes.
Grp78 heterozygosity increases energy expenditure and attenuates HFD-induced obesity. Grp78+/- mice are resistant to diet-induced hyperinsulinemia, liver steatosis, white adipose tissue (WAT) inflammation, and hyperglycemia.
Why this rating
High-quality in vivo mouse model with rigorous metabolic phenotyping (clamps, indirect calorimetry), though not human clinical data.
Source
<i>Grp78</i> Heterozygosity Promotes Adaptive Unfolded Protein Response and Attenuates Diet-Induced Obesity and Insulin Resistance
Risheng Ye et al. · Diabetes · 2009
DOI 10.2337/db09-0755
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