Background: Predominance of adiposity and diabetes is dramatically expanding. Asprosin, a novel adipokine, serve as cross-organ messenger, linking adipose tissue with skeletal muscle. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump mediates Ca2+ entry from sarcoplasm back to its lumen. Sarcolipin (SLN) is an uncoupler of SERCA pump, playing an important role in muscle-based thermogenesis. Aim: We aimed to explore the role of exercise (EX) and/or liposomal curcumin (LP-CUR) to counteract asprosin in the pathogenesis of adiposity by modulating the SLN/SERCA proteins. Materials and method: This study was conducted for 8 weeks through 5 Groups of rats. The control group fed normal diet. While, the others were fed high-fat diet (HFD) either alone HFD group, or with performing EX by running on treadmill at 20 m/min for 1 hour/day, 4 days/week, or received LP-CUR 10 mg/kg/day, or combination of both.