Hexanoic acid improves metabolic health in mice fed high-fat diet.

Ikeda, T.; Nishimoto, Y.; Ichikawa, D.; Matsunaga, T.; Kawauchi, A.; Kimura, I.

doi:10.1101/2025.02.20.639216

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bioRxiv · 10.1101/2025.02.20.639216

Hexanoic acid improves metabolic health in mice fed high-fat diet.

Ikeda, T.·Nishimoto, Y.·Ichikawa, D.·Matsunaga, T.·Kawauchi, A.·Kimura, I.

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Abstract

BackgroundOverweight and obesity is currently a worldwide problem with undesirable health consequences such as type 2 diabetes. Therefore, much attention has been paid to preventing obesity through diet. Free fatty acids (FFAs) are an important energy source, and they also serve as signaling molecules in many biological processes leading to an increased energy expenditure and insulin secretion. Short-chain fatty acids (SCFAs) such as acetic, propionic and butyric acid are the bioactive metabolites produced by gut microbes, and their beneficial effects on host metabolism are well-studied. In addition, medium-chain fatty acids (MCFAs) such as octanoic and decanoic acid also play a positive role in regulating lipid and glucose metabolisms. However, the effects of hexanoic acid on metabolism are poorly understood. Therefore, this study investigated the role of hexanoic acid on lipid and glucose metabolism in mice. MethodsMale C57BL/6J mice were fed normal chow diet, high-fat diet (HFD), HFD-containing 5% butyric acid or HFD-containing 5% hexanoic acid for 4 weeks, and the effects of hexanoic acid on lipid and glucose metabolism were examined. ResultsButyric acid and hexanoic acid prevented body weight gain and fat accumulation in white adipose tissues under HFD-feeding. In addition, both FFAs suppressed the elevated plasma levels of non-esterified fatty acid (NEFA) and hepatic triglyceride content induced by HFD. The expression levels of genes involved in fatty acid biosynthesis were decreased in white adipose tissues by oral supplementation of butyric acid or hexanoic acid. Mice fed HFD also exhibited hyperglycemia and hyperinsulinemia, and these impaired glucose metabolisms improved by hexanoic acid. Hexanoic acid increased the expression levels of genes associated with gluconeogenesis, and improved insulin sensitivity in mice fed HFD. ConclusionsThis study highlights the importance of hexanoic acid in improvement of lipid and glucose metabolisms. Thus, our findings provide insight into the development of functional foods which prevent obesity-related disease such as type 2 diabetes.

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Ikeda, T., Nishimoto, Y., Ichikawa, D., Matsunaga, T., Kawauchi, A., Kimura, I.. 2025-02-27. Hexanoic acid improves metabolic health in mice fed high-fat diet.. https://doi.org/10.1101/2025.02.20.639216

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