article · Antioxidants
Adipotoxicity plays a major role in insulin resistance and type 2 diabetes, with the gut and adipose tissues acting as key therapeutic targets. This study examined how gut metabolites derived from fermented soursop fruit and peel influence fat tissue dysfunction. Researchers fermented soursop pulp and peel using rat faecal microbiota, then applied the resulting metabolites to rat white adipose tissue exposed to high fructose levels. The fermentation altered the faecal metabolome, enriching compounds linked to lipid and sterol metabolism. In the adipose tissue, fructose induced metabolic dysfunction, impaired antioxidant and detoxification pathways, and increased inflammatory enzyme activity. Soursop-derived metabolites reversed these adverse changes in a dose-dependent manner, restoring glucose handling, cellular detoxification, and fatty acid metabolism more effectively than the reference antioxidant gallic acid. These findings show that soursop gut metabolites help protect fat tissue homeostasis.
Dietary fructose can disrupt fat tissue function, driving cellular stress, inflammation, and metabolic disorders such as type 2 diabetes. Understanding how gut bacteria transform common fruits like soursop into protective compounds provides crucial insight into diet-microbiome interactions. This work highlights how food-derived molecules might be harnessed to preserve metabolic health and counteract dietary triggers of obesity-related disease.
This research is at an early experimental stage, relying on in vitro fermentation and ex vivo tissue models. The findings could eventually interest nutraceutical developers, functional food manufacturers, and dietary supplement companies seeking natural ingredients to support metabolic health and manage adipose dysfunction. Substantial further work, including in vivo animal trials and human clinical studies, will be necessary before any commercial dietary products or formulations can be realised.
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Adipotoxicity is a major contributor to insulin resistance and type 2 diabetes, and increasing evidence highlights the gut–adipose axis as a promising therapeutic target. Soursop (Annona muricata) is rich in phytochemicals that can be biotransformed by the gut microbiota into bioactive metabolites with metabolic benefits. The present study investigated whether metabolites generated by in vitro fecal fermentation of soursop fruit (SWSF) and peel (SWSFP) protect against fructose-induced adipotoxicity. SWSF and SWSFP were fermented with rat fecal microbiota, and the resulting metabolites were evaluated in an ex vivo fructose-induced adipotoxicity model using perigonadal white adipose tissue. Activities of enzymes involved in glucose metabolism, the polyol pathway, glutathione metabolism, glyoxalase-1 activity, purinergic signaling, and inflammatory lipid metabolism were determined. GC–MS-based metabolomics and pathway enrichment analyses were performed on fecal and adipose tissues. Soursop fermentation significantly remodeled the fecal metabolome, enriching metabolites associated with fatty acid metabolism, glycerolipid metabolism, β-oxidation, sterol metabolism, and arachidonic acid metabolism. Fructose-induced adipotoxicity disrupted glucose metabolism, activated the polyol pathway, impaired glutathione metabolism and glyoxalase-1 activity, suppressed ATPase and ENTPDase activities, and elevated 5-LOX and 12/15-LOX activities. Treatment with soursop-enriched fecal metabolites significantly reversed these alterations in a dose-dependent manner. Adipose metabolomics further demonstrated restoration of pathways associated with fatty acid biosynthesis, mitochondrial β-oxidation, glycerolipid metabolism, steroid biosynthesis, and polyunsaturated fatty acid metabolism, indicating improved lipid homeostasis and reduced inflammatory lipid signaling. SWSF and SWSFP generally exhibited greater metabolic protection than the reference antioxidant compound, gallic acid. Soursop-derived gut metabolites attenuate fructose-induced adipotoxicity by coordinately restoring glucose metabolism, redox homeostasis, carbonyl detoxification, purinergic signaling, and lipid metabolism through the gut–adipose axis. These results suggest soursop as a potential functional food for preventing and managing adipose tissue dysfunction and metabolic disorders.
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DOI: 10.3390/antiox15091106
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