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May 14, 2026Physiology0 citations

Characterization of caffeine-mediated effects on hepatic metabolism in adult zebrafish

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EWEmma WanstrathSCSamantha St. Clair

Key Points

  • This study aims to characterize how caffeine influences glucose and fat metabolism in adult zebrafish under varying dietary conditions.
  • Utilized male and female adult zebrafish as a model system.
  • Administered caffeine supplementation at 0.1 and 0.13 mg/day for 6 weeks.
  • Analyzed hepatic expression levels of genes involved in lipid synthesis and inflammatory response.
  • Zebrafish gained less weight on a standard diet with caffeine compared to unsupplemented fish.
  • Caffeine supplementation increased fasting blood glucose levels.
  • 0.13 mg/day caffeine may be toxic to adult zebrafish.

Abstract

Approximately 85% of Americans consume at least one caffeinated beverage daily. In addition to promoting the dreaded midday crash, this habit alters glucose and fat metabolism. Caffeine regulates hepatic fat production by inhibiting fatty acid synthase (fasn), an enzyme involved in de novo lipogenesis. Interestingly, caffeine consumption promotes insulin resistance in insulin sensitive individuals and prevents insulin resistance in obese populations. Utilizing male and female adult zebrafish as a model system, our study assesses how caffeine differentially regulates glucose and fat metabolism under standard and high fat feeding conditions. Consistent with previous studies, we report that zebrafish gain less weight when fed a standard diet supplemented with caffeine (in both 0.1 and 0.13 mg caffeine/day) for 6 weeks, relative to un-supplemented fish. Oral caffeine supplementation increased fasting blood glucose levels. We also report that 0.13 mg/day oral caffeine supplementation may be toxic to adult zebrafish. Samples have been collected for analysis of hepatic expression levels of genes involved in lipid synthesis and inflammatory response. This process will be repeated with fish consuming a high fat diet, as well as supplementing diets with freeze dried beverages from local coffee shops. We hypothesize that high levels of caffeine consumption differentially regulate fat and glucose metabolism by eliciting variable inflammatory responses. Overall this data expands our understanding of how caffeine influences the physiology of various populations, and could potentially highlight a role for caffeine in staving off metabolic disease. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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Cite This Study

Wanstrath et al. (2026) studied this question.

synapsesocial.com/papers/6a05680ea550a87e60a20731https://doi.org/10.1152/physiol.2026.41.s1.2300542
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