Crocin inhibits obesity <i>via</i> AMPK-dependent inhibition of adipocyte differentiation and promotion of lipolysis

Abstract

Obesity has become a severe public health problem worldwide. Crocin, a natural product, has been reported to have a number of pharmacological activities, including antiinflammatory, 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.

The Effect of Crocin Supplementation on Glycemic Control, Insulin Resistance and Active AMPK Levels in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…AMPK is a central regulator of energy metabolism and nutrient status that regulates glucose and lipid metabolism. Downregulation of AMPK is associated with obesity, metabolic syndrome and diabetes mellitus (44). In our study, oral administration of crocin could not alter the active form of AMPK enzyme compared to placebo, moreover no signi cant changes were observed within each group.…”

Pathogenic Microenvironment from Diabetic–Obese Visceral and Subcutaneous Adipocytes Activating Differentiation of Human Healthy Preadipocytes Increases Intracellular Fat, Effect of the Apocarotenoid Crocetin

“…Saffron contains several bioactive compounds, of which crocins (crocetin esters) also exert antiadipogenic activity. Gu et al, reported that this effect of crocins occurred by activation of AMP-activated protein kinase (AMPK) [51], which is a fundamental sensor and modulator of metabolism. Rayalam et al, reported that the activation of AMPK inhibits differentiation of 3T3-L1 adipocytes, by blocking the expression of transcription factors, such as C/EBPα and PPARγ among others factors [52].…”

The effect of crocin supplementation on glycemic control, insulin resistance and active AMPK levels in patients with type 2 diabetes: a pilot study

“…AMPK is a central regulator of energy metabolism and nutrient status that regulates glucose and lipid metabolism. Downregulation of AMPK is associated with obesity, metabolic syndrome and diabetes mellitus [ 44 ]. In our study, oral administration of crocin could not alter the active form of AMPK enzyme compared to placebo, moreover no significant changes were observed within each group.…”