WHRadjBMI-increasing alleles at the RSPO3 locus increase RSPO3 expression in subcutaneous adipocytes, leading to reduced lower-body fat and enlarged gluteal adipocytes.
RSPO3 is a key determinant of peripheral adipose tissue storage capacity, regulating body fat distribution through depot-specific effects on adipocyte biology.
Effect estimate: β 0.05
p-value: p=3×10^-8
Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase RSPO3 expression in subcutaneous adipocytes. These variants are also associated with reduced lower-body fat, enlarged gluteal adipocytes and insulin resistance. Based on human cellular studies RSPO3 may limit gluteofemoral adipose tissue (AT) expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis. RSPO3 may also promote upper-body fat distribution by stimulating abdominal adipose progenitor (AP) proliferation. The distinct biological responses elicited by RSPO3 in abdominal versus gluteal APs in vitro are associated with differential changes in WNT signalling. Zebrafish carrying a nonsense rspo3 mutation display altered fat distribution. Our study identifies RSPO3 as an important determinant of peripheral AT storage capacity.
Loh et al. (Wed,)은 체지방 분포에 관한 연구(n=4,571)를 수행했습니다. RSPO3 WHRadjBMI 증가 대립 유전자와 조상 대립 유전자가 Android/gynoid 지방 비율에 미치는 영향을 평가했습니다(β 0.05, p=3×10^-8). RSPO3 유전자좌에서 WHRadjBMI 증가 대립 유전자는 피하 지방세포에서 RSPO3 발현을 증가시키고, 그 결과 하체 지방이 감소하고 둔부 지방세포가 커집니다.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: