Fig. (IMAGE)
Caption
Body fat levels vary due to physiological, pathological, environmental, hormonal, and genetic factors. Our study identifies HSP47 – abundant in fat tissues – as a key determinant of body adiposity. HSP47 expression increases with feeding, overeating, and obesity, and decreases with fasting, exercise, calorie restriction, bariatric surgery, and cachexia. It significantly correlates with body fat traits, such as body fat mass, BMI, waist, and hip circumferences, and is regulated by insulin and glucocorticoids. In humans, increased HSP47 gene expression by its intron or synonymous variants, is associated with higher body fat. Mice lacking HSP47 show significantly lower body fat. Mechanistically, HSP47 promotes collagen protein dynamics, including folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPARγ protein from proteasomal degradation, partly related to MDM2. These findings highlight the significant role of HSP47 in body adiposity. This study provides valuable insights into the individual variability and differences in body adiposity traits observed in diverse circumstances.
Credit
2023 Jihoon Shin et al., HSP47 levels determine the degree of body adiposity. Nature Communications
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CC BY