Obesity has become a severe public health problem worldwide. Crocin, a natural product, has been reported to have a number of pharmacological activities, including anti-inflammatory, anti-cancer, neuroprotective, antihypertensive, and cardioprotective action. The aims of the current study were to identify the beneficial effects of crocin on obesity, adipocyte differentiation, and lipolysis and to evaluate the possible role of AMPK. Results indicated that crocin significantly increased AMPK phosphorylation in differentiated adipocytes in vitro and in adipose tissue in db/db mice. Crocin reduced lipid accumulation in differentiated adipocytes. In addition, crocin inhibited the expression of mRNA of important adipogenesis-related regulators, including CEBPα, CEBPβ, PPARγ, aP2, FAS, and CD36, in both differentiated adipocytes and adipose tissue in db/db mice. Crocin increased the expression of mRNA of key lipolysis-associated factors, including PPARα, LPL, and HSL, in both differentiated adipocytes and adipose tissue in db/db mice. In adipocytes, knockdown of AMPK significantly suppressed the crocin-induced inhibition of adipocyte differentiation and increase in lipolysis. BML-275 is an inhibitor of AMPK. In adipose tissue in db/db mice, BML-275 suppressed crocin-induced inhibition of fat formation and alleviation of a metabolic disorder. The current results suggest that crocin alleviates obesity in db/db mice and that it inhibits adipocyte differentiation in preadipocytes. Crocin inhibits adipogenesis and promotes lipolysis via activation of AMPK. Therefore, crocin may have promise as an option for the clinical treatment for obesity and associated metabolic diseases.
Keywords: AMPK; Obesity; adipocyte differentiation; crocin; lipolysis.