Theobromine, a
methylxanthine present in cocoa, has been shown to possess many beneficial pharmacological properties such as anti-oxidative stress, anti-inflammatory property, and anti-microbial activity. In this study, we investigated the effects of
theobromine on
nonalcoholic fatty liver disease (
NAFLD) and the possible underlying mechanisms in vivo and in vitro. The results showed that
theobromine reduced
body weight and fat mass and improved
dyslipidemia.
Theobromine mitigated liver injury and significantly reduced hepatic
triglyceride level in mice with
obesity. Histological examinations also showed hepatic steatosis was alleviated after
theobromine treatment. Furthermore,
theobromine reversed the elevated
mRNA and
protein expression of
SREBP-1c, FASN, CD36, FABP4, and the suppressed expression of PPARĪ± and CPT1a in the liver of mice with
obesity, which were responsible for lipogenesis,
fatty acid uptake, and
fatty acid oxidation respectively. In vitro,
theobromine also downregulated
SREBP-1c, FASN, CD36, FABP4 and upregulated PPARĪ± and CPT1a
mRNA and
protein levels in hepatocytes in a dose-dependent manner, while these changes were reversed by
L-leucine, a
mammalian target of rapamycin (mTOR) agonist. The present study demonstrated that
theobromine improved
NAFLD by inhibiting lipogenesis and
fatty acid uptake and promoting
fatty acid oxidation in the liver and hepatocytes, which might be associated with its suppression of mTOR signaling pathway. Novelty:
Theobromine protects against high-fat diet - induced
NAFLD.
Theobromine inhibits lipogenesis and
fatty acid uptake and promotes
fatty acid oxidation in the liver and hepatocytes via inhibiting mTOR signaling pathway.