The Journal of nutritional biochemistryNov 8, 2021

Theobromine helps turn white fat cells into energy-burning beige fat cells by activating PPARγ

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

Dietary supplementation of theobromine (TB) significantly increased skin temperature in the inguinal region of mice.

TB induced the expression of UCP1 protein, which is involved in energy expenditure.
Theobromine increased mitochondrial marker protein levels in subcutaneous adipose tissue but not in visceral adipose tissue.
Microarray analysis revealed that TB upregulated multiple genes associated with thermogenesis and beige adipocytes in subcutaneous adipose tissue.
In primary adipocytes derived from mice, TB enhanced UCP1 protein expression and mitochondrial mass in a manner dependent on PPARγ ligands.
TB increased phosphorylation levels of PPARγ coactivator 1α without affecting its overall protein levels.

Simplified

The adipocytes play an important role in driving the obese-state-white adipose tissue (WAT) stores the excess energy as fat, wherein brown adipose tissue (BAT) is responsible for energy expenditure via the thermoregulatory function of uncoupling protein 1 (UCP1)-the imbalance between these two onsets obesity. Moreover, the anti-obesity effects of brown-like-adipocytes (beige) in WAT are well documented. Browning, the process of transformation of energy-storing into energy-dissipating adipocytes, is a potential preventive strategy against obesity and its related diseases. In the present study, to explore an alternative source of natural products in the regulation of adipocyte transformation, we assessed the potential of theobromine (TB), a bitter alkaloid of the cacao plant, inducing browning in mice (in vivo) and primary adipocytes (in vitro). Dietary supplementation of TB significantly increased skin temperature of the inguinal region in mice and induced the expression of UCP1 protein. It also increased the expression levels of mitochondrial marker proteins in subcutaneous adipose tissues but not in visceral adipose tissues. The microarray analysis showed that TB supplementation upregulated multiple thermogenic and beige adipocyte marker genes in subcutaneous adipose tissue. Furthermore, in mouse-derived primary adipocytes, TB upregulated the expression of the UCP1 protein and mitochondrial mass in a PPARγ ligand-dependent manner. It also increased the phosphorylation levels of PPARγ coactivator 1α without affecting its protein expression. These results indicate that dietary supplementation of TB induces browning in subcutaneous WAT and enhances PPARγ-induced UCP1 expression in vitro, suggesting its potential to treat obesity.

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Theobromine helps turn white fat cells into energy-burning beige fat cells by activating PPARγ

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