Collagen-specific molecular chaperone Hsp47 in inguinal white adipose tissue promotes high-fat diet-induced inflammatory gene expression in male mice

A chronic high-fat diet (HFD) leads to obesity through a process involving adipocyte hypertrophy, hyperplasia, induction of pro-inflammatory gene expression, and ultimately fibrosis that impairs systemic health. Adipocytes are surrounded by an extracellular matrix (ECM) containing collagen. The interaction between adipocytes and the ECM regulates adipocyte turnover under both physiological and HFD conditions. Previous studies have shown that the collagen-specific molecular chaperone Hsp47 (SerpinH1) increases with overfeeding and decreases with short-term fasting. Hsp47 affects adipocyte size through collagen-integrin interactions. However, the long-term contribution of Hsp47 under chronic HFD conditions remains unclear, particularly whether there are depot-specific differences between subcutaneous inguinal white adipose tissue (ingWAT) and visceral epididymal white adipose tissue (epiWAT). In this study, mice fed an HFD for 12 weeks exhibited increased Hsp47 mRNA and protein specifically in adipose tissue. Adipocyte-specific Hsp47 knockout (aKO) mice exhibited reduced adipocyte size and decreased fibrosis markers and pro-inflammatory gene expression, specifically in ingWAT, with minimal impact in epiWAT. Serum analysis revealed that the metabolic deterioration induced by an HFD was alleviated in Hsp47 aKO mice. These results suggest that increased Hsp47 in ingWAT during an HFD contributes to adipose tissue dysfunction by promoting pro-inflammatory gene expression. These findings highlight Hsp47 as a potential therapeutic target for obesity-related metabolic disorders.