Forskning

August 21, 2013

Caffeine stimulates hepatic lipid metabolism via autophagy-lysosomal pathway

R A Sinha et al, 2013, Caffeine stimulates hepatic lipid metabolism via autophagy-lysosomal pathway, Hepatology, Accepted Article, published online ahead of print.

ABSTRACT:
Caffeine is one of the worlds most consumed drugs. Recently, several studies showed that its consumption is associated with lower risk for non-alcoholic fatty liver disease (NAFLD), an obesity-related condition that recently has become the major cause of liver disease worldwide. Although caffeine is known to stimulate hepatic fat oxidation, its mechanism of action on lipid metabolism is still not clear. Here, we show that caffeine surprisingly is a potent stimulator of hepatic autophagic flux. Using genetic, pharmacological, and metabolomic approaches, we demonstrate that caffeine reduces intra-hepatic lipid content and stimulates β-oxidation in hepatic cells and liver via an autophagy-lysosomal pathway. Furthermore, caffeine induced autophagy involved downregulation of mTOR signaling and alteration in hepatic amino acids and sphingolipid levels. In mice fed a high fat diet, caffeine markedly reduces hepatosteatosis and concomitantly increases autophagy and lipid uptake in lysosomes. Conclusion: Taken together, these results provide novel insight into caffeine’s lipolytic actions through autophagy in mammalian liver and its potential beneficial effects in NAFLD.