Methylxanthine Derivative-Rich Cacao Extract Suppresses Differentiation of Adipocytes through Downregulation of PPARγ and C/EBPs

Abstract

Cacao extract (CE) consumption has beneficial effects on human health, such as lowering the risk of obesity. However, the underlying molecular mechanism for the anti-obesity effect of CE remains incompletely understood. Here, we used a 50% aqueous alcohol extract of cacao mass, which is rich in methylxanthine derivatives (about 11%) and poor in flavan-3-ols (less than 1%), and assessed the suppression effects of this extract on adipocyte differentiation to investigate the anti-obesity mechanism. CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK.

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“…Nowadays, the reported effects of chocolate intake on body weight are contradictory: while it has been shown that chocolate supplementation does not increase or reduce body weight, subsequent subgroup analyses following dose-response evaluations indicated that chocolate consumption (as compared to no chocolate) resulted in waist circumference reduction. 15 Congruently, experimental studies performed in adipose tissue from mice and in murine cell lines show that cacao decreases fat accumulation in adipocytes by decreasing lipogenic enzyme expression 27 while increasing lipolytic enzyme expression. 28 Considering the so-called 3,500-calorie rule that estimates that increasing caloric intake by 500 kcal per day, or 3500 kcal per week would result in 1 lb of weight gain per week, these postmenopausal females should have gained more than 2 lb (~1 kg) in each chocolate intervention (2 wk × 7d × 542 kcal = 7588 kcal) if there would be no differences in ad libitum intake or energy expenditure.…”

“…Nowadays, the reported effects of chocolate intake on body weight are contradictory: while it has been shown that chocolate supplementation does not increase or reduce body weight, subsequent subgroup analyses following dose‐response evaluations indicated that chocolate consumption (as compared to no chocolate) resulted in waist circumference reduction 15 . Congruently, experimental studies performed in adipose tissue from mice and in murine cell lines show that cacao decreases fat accumulation in adipocytes by decreasing lipogenic enzyme expression 27 while increasing lipolytic enzyme expression 28 …”

Effects of Lactobacillus Casei YBJ02 on Lipid Metabolism in Hyperlipidemic Mice

“…PPARγ is an important factor influencing differentiation from precursor adipocytes to mature adipocytes. It is essential for the adipocyte expression in fat differentiation, which is mainly expressed in adipose tissue and can control fat oxidation (Yamashita, Mitani, Wang, & Ashida, ). FAS converts the nutrients absorbed in mice into fatty acids, which can significantly increase the amount of triglyceride synthesis (Yu et al., ).…”

Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism

“…The treatment with flavan-3-ol could increase the sympathetic nerve activity, adrenaline contents, and the mRNA expression levels of UCP-1 in mice, suggesting that flavan-3-ol had a positive effect on lipid metabolism in mice, thereby affecting the proliferation and differentiation of brown adipocytes and related regulatory processes of WFB. Moreover, flavan-3-ols could also increase the concentration of catecholamines in plasma, which induce WFB by stimulating the activation of β-adrenergic receptors and mediating the protein kinase A signal transduction, thereby promoting the fat metabolism-related processes [ 94 ].…”