3-(4-Hydroxy-3-methoxyphenyl)propionic Acid Produced from 4-Hydroxy-3-methoxycinnamic Acid by Gut Microbiota Improves Host Metabolic Condition in Diet-Induced Obese Mice

Abstract

4-Hydroxy-3-methoxycinnamic acid (HMCA), a hydroxycinnamic acid derivative, is abundant in fruits and vegetables, including oranges, carrots, rice bran, and coffee beans. Several beneficial effects of HMCA have been reported, including improvement of metabolic abnormalities in animal models and human studies. However, its mitigating effects on high-fat diet (HFD)-induced obesity, and the mechanism underlying these effects, remain to be elucidated. In this study, we demonstrated that dietary HMCA was efficacious against HFD-induced weight gain and hepatic steatosis, and that it improved insulin sensitivity. These metabolic benefits of HMCA were ascribable to 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) produced by gut microbiota. Moreover, conversion of HMCA into HMPA was attributable to a wide variety of microbes belonging to the phylum Bacteroidetes. We further showed that HMPA modulated gut microbes associated with host metabolic homeostasis by increasing the abundance of organisms belonging to the phylum Bacteroidetes and reducing the abundance of the phylum Firmicutes. Collectively, these results suggest that HMPA derived from HMCA is metabolically beneficial, and regulates hepatic lipid metabolism, insulin sensitivity, and the gut microbial community. Our results provide insights for the development of functional foods and preventive medicines, based on the microbiota of the intestinal environment, for the prevention of metabolic disorders.

Tibet Kefir Milk Regulated Metabolic Changes Induced by High-Fat Diet via Amino Acids, Bile Acids, and Equol Metabolism in Human-Microbiota-Associated Rats

“…For instance, 10-hydroxy- cis -12-octadecenoic acid is an initial linoleic acid-related gut-microbial metabolite, which attenuates HFD-induced obesity in mice by improving the metabolic profile via free fatty acid receptors and by enhancing intestinal barrier function . 3-(4-Hydroxy-3-methoxyphenyl) propionic acid, produced by gut microbiota, is a metabolically beneficial metabolite that regulates hepatic lipid metabolism and insulin sensitivity . There is a bidirectional regulation between gut microbiota and host metabolism.…”

“…18 3-(4-Hydroxy-3-methoxyphenyl) propionic acid, produced by gut microbiota, is a metabolically beneficial metabolite that regulates hepatic lipid metabolism and insulin sensitivity. 19 There is a bidirectional regulation between gut microbiota and host metabolism. Tryptophan and its endogenous host metabolites have modulatory effects on gut microbial composition and microbial functions.…”

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension

“…Third, the Clostridium cluster IX levels were also significantly lower (p=0.045) in the PH group than in the non-PH-G. This cluster is said to have many strains that produce propionic acid; however, for most strains, the effect on the host and function in the human intestines remains largely unknown (25,26). In light of our results, these topics represent further questions that should be explored.…”

Nutrition, Bioactive Components, and Hepatoprotective Activity of Fruit Vinegar Produced from Ningxia Wolfberry

“…p -hydroxybenzoic acid is mainly obtained from the oxidation of 2-(4-hydroxyphenyl) ethanol in the process of acetic acid fermentation [ 41 ]. It was found that 3-(4-hydroxy-3-methoxyphenyl) propionic acid has anti-oxidative activity, which was related to anti-inflammatory effects and regulation of lipid metabolism [ 42 ]. Chlorogenic acid, as a polyphenol monomer, was as abundant in vinegar as other fruit vinegar [ 10 ].…”