論文 - 詳細
| RRC ID | 77399 |
|---|---|
| 著者 | Shin J, Toyoda S, Okuno Y, Hayashi R, Nishitani S, Onodera T, Sakamoto H, Ito S, Kobayashi S, Nagao H, Kita S, Otsuki M, Fukuhara A, Nagata K, Shimomura I. |
| タイトル | HSP47 levels determine the degree of body adiposity. |
| ジャーナル | Nat Commun |
| Abstract |
Adiposity varies among individuals with the influence of diverse physiological, pathological, environmental, hormonal, and genetic factors, but a unified molecular basis remains elusive. Here, we identify HSP47, a collagen-specific chaperone, as a key determinant of body adiposity. HSP47 expression is abundant in adipose tissue; increased with feeding, overeating, and obesity; decreased with fasting, exercise, calorie restriction, bariatric surgery, and cachexia; and correlated with fat mass, BMI, waist, and hip circumferences. Insulin and glucocorticoids, respectively, up- and down-regulate HSP47 expression. In humans, the increase of HSP47 gene expression by its intron or synonymous variants is associated with higher body adiposity traits. In mice, the adipose-specific knockout or pharmacological inhibition of HSP47 leads to lower body adiposity compared to the control. Mechanistically, HSP47 promotes collagen dynamics in the folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPARγ protein from proteasomal degradation, partly related to MDM2. The study highlights the significance of HSP47 in determining the amount of body fat individually and under various circumstances. |
| 巻・号 | 14(1) |
| ページ | 7319 |
| 公開日 | 2023-11-11 |
| DOI | 10.1038/s41467-023-43080-x |
| PII | 10.1038/s41467-023-43080-x |
| PMID | 37951979 |
| PMC | PMC10640548 |
| MeSH | Adiposity* Animals Collagen / metabolism HSP47 Heat-Shock Proteins* / genetics Humans Mice Molecular Chaperones / metabolism Obesity / genetics |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 17 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC10972 |