Caffeine and liver disease in mice
What it found
In mice with a fatty liver disease called MASH, caffeine reduced liver fat, inflammation and early scarring.
The authors say this happens through a liver protein called Dusp9.
What they found
Animal and lab studies
Liver fat and blood fats
In mice on the long-term high-fat, high-carb diet, caffeine lowered liver fat, serum triglycerides, total cholesterol and LDL. It also reduced body weight and liver weight.
Blood sugar and insulin
The high-fat diet raised fasting blood glucose and insulin and increased insulin resistance. Caffeine brought these back toward normal in the mice.
Liver inflammation and scarring
Caffeine reduced liver injury markers, macrophage infiltration and inflammatory genes. It also reduced liver fibrosis, collagen and hydroxyproline in both mouse models.
Dusp9 as caffeine target
The liver protein Dusp9 was suppressed by the high-fat diet but restored by caffeine. Lab tests showed caffeine binds directly to Dusp9 and increases its stability.
Dusp9 knockdown effects
When Dusp9 was knocked down in mice or silenced in liver cells, caffeine's benefits on liver fat, glucose metabolism, inflammation and fibrosis were largely lost.
Downstream signaling
Caffeine inactivated the ASK1-p38/JNK signaling pathway, which is involved in inflammation and cell death. This effect was reversed when Dusp9 was absent.
What the authors conclude
“Our study highlights the multifaceted benefits of CAFF in treating MASH by rescuing hepatic Dusp9 expression, thereby reversing glycolipid metabolism disorders, liver inflammation, and fibrosis.”
Also in their conclusions
- They conclude that caffeine alleviates MASH by rescuing hepatic Dusp9, which in turn controls fat production, liver inflammation and fibrosis.
- They say their findings provide experimental evidence supporting the clinical and daily use of caffeine and black coffee in managing MASH patients.
- They recommend further trials with higher dosages and longer duration.
How it was done
Coffee and caffeine have been linked to liver benefits in people, but how caffeine might work in the liver was not clear. The authors wanted to find the specific protein target behind these effects.
Mice were fed a high-fat, high-carbohydrate diet for 36 weeks to cause MASH, then given caffeine in drinking water (75 mg/kg) by gavage for the final 6 weeks. A second mouse model used a high-fat diet plus carbon tetrachloride injections for 6 weeks. Human liver cells (THLE-2) loaded with fatty acids were also treated with caffeine at 0.25, 0.5 and 1 mM.
What it can’t tell you
- These are animal and cell studies. They cannot show whether the same effects happen in people.
- The mice were given caffeine by gavage at a specific dose, so the results may not apply to how people drink coffee.
- The study cannot prove that caffeine prevents or treats MASH in humans.
Who paid
- Conflicts
- Declaration of competing interest The authors disclose no conflicts of interest.
- Authors work at
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China; Columbia University Irving Medical Center, USA
The paper
- Title
- Caffeine ameliorates metabolic-associated steatohepatitis by rescuing hepatic Dusp9
- Type
- Study
- Evidence
- Animals and lab studies
- Summarised from
- Full text
- Cite
- Xin X, Chen C, Xu X, et al (2025). Caffeine ameliorates metabolic-associated steatohepatitis by rescuing hepatic Dusp9. Redox biology. doi:10.1016/j.redox.2025.103499Free full textPubMed 39879738DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error