Adipocyte‐Derived KIF13B Aggravates Obesity‐Associated Metabolic Dysfunction via LRP1/PPARγ Signaling

Obesity is driven by maladaptive adipose expansion, yet the intracellular machinery linking motor protein‐associated intracellular regulation to adipogenic transcription remains incompletely understood. Here, we identify adipocyte‐derived kinesin family member 13B (KIF13B) as a regulator of obesity‐associated metabolic dysfunction through lipoprotein receptor‐related protein 1 (LRP1)/peroxisome proliferator‐activated receptor γ (PPARγ) signaling. KIF13B expression is markedly upregulated in adipose tissue from humans and mice with obesity. Adipocyte‐specific Kif13b deletion protected mice from high‐fat diet‐induced weight gain, adipose expansion and inflammation, dyslipidemia, insulin resistance, and hepatic steatosis, while promoting thermogenic remodeling. In mice with established diet‐induced obesity, adeno‐associated virus serotype 9 (AAV9)‐mediated adipocyte‐targeted KIF13B knockdown improved adipose inflammation, lipid and glucose homeostasis, and liver injury; selected metabolic benefits were also observed in ob/ob mice. Mechanistically, KIF13B facilitates PPARγ‐responsive transcriptional activity and adipogenic lipid accumulation via LRP1. This proadipogenic KIF13B/LRP1/PPARγ axis is further supported by human adipose transcriptomic analyses, which reveal positive correlations among its components in obesity and Type 2 diabetes. These findings define a previously unrecognized KIF13B–LRP1–PPARγ axis linking intracellular trafficking to pathological adipocyte remodeling and support adipocyte KIF13B as a potential therapeutic target for obesity‐associated metabolic disease.