Dietary cannabidiol oil mitigates metabolic dysfunction in mice with high-fat diet-induced obesity

Metabolic syndrome (MetS) is a widespread health concern driven largely by lifestyle behaviors such as dietary choices and physical inactivity. Excessive caloric intake promotes adiposity and dysregulation of metabolic signaling in adipose tissue. This study employed a mouse model of diet-induced obesity to evaluate the ability of cannabidiol (CBD), a cannabis-derived phytochemical, to mitigate metabolic dysfunction. Five-week-old mice received a standard diet or a high-fat diet (HF) with or without CBD (25 mg/kg bw) for 9 weeks. CBD supplementation reduced weight gain and lowered serum glucose concentration in HF mice. These improvements were accompanied by reduced white adipose tissue mass and smaller adipocyte size. Additionally, CBD treatment recovered protein levels of key metabolic regulators, including peroxisome proliferator-activated receptor-γ coactivator 1 alpha and Sirtuin 1, in both inguinal and epididymal adipose tissues. Consistently, CBD supplementation upregulated the mRNA expression of Prdm16 and promoted uncoupling protein 1 at both mRNA and protein levels, showing the browning of adipose tissues. Upstream, CBD supplementation increased transient receptor potential vanilloid 1 (TRPV1) in HF mice at both the mRNA and protein levels, which possibly helped orchestrate the observed improvements. In summary, dietary CBD mitigates weight gain and improves the metabolic health of HF-challenged mice, potentially through the promotion of white adipose tissue browning.