Hepatic Steatosis Can Be Partly Generated by the Gut Microbiota-Mitochondria Axis via 2-Oleoyl Glycerol and Reversed by a Combination of Soy Protein, Chia Oil, Curcumin and Nopal.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat-sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed the HFS diet for 7 months. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance, lipogenic and antioxidant enzymes, hepatic 2-OG measurement, and mitochondrial function of the rats were evaluated. Also, the effect of the consumption of functional food with an HFS diet was assessed. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of the HFS diet in Wistar rats caused oxidative stress, hepatic steatosis, and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. The addition of functional foods to the diet modified the gut microbiota, reducing Blautia producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. To use 2-OG as a biomarker, this metabolite was measured in healthy subjects or with MASLD, and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis.

Epigenetic reprogramming of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes.

Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes (Ad). This study aimed to investigate the impact of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from rats on a high-fat sucrose (HFS) diet displayed reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than the control (C) group. Mitochondrial analysis revealed heightened activity in undifferentiated ASC-HFS but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 profile in ASCs on genes related to adipogenesis, mitochondrial function, inflammation, and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations, confirming the upregulation of genes associated with inflammatory and immunomodulatory pathways. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. Overall, the HFS diet induced significant epigenetic and transcriptomic changes in ASCs, impairing differentiation and causing dysfunctional adipocyte formation.NEW & NOTEWORTHY Obesity is associated with the development of chronic diseases like metabolic syndrome and type 2 diabetes, and adipose tissue plays a crucial role. In a rat model, our study reveals how an obesogenic environment primes adipocyte precursor cells, leading to epigenetic changes that affect inflammation, adipogenesis, and mitochondrial activity after differentiation. We highlight the importance of histone modifications, especially the trimethylation of histone H3 to lysine 4 (H3K4me3), showing its influence on adipocyte expression profiles.

Nutritional Composition and Bioactive Compounds of Quelites Consumed by Indigenous Communities in the Municipality of Juquila Vijanos, Sierra Norte of Oaxaca, Mexico.

The indigenous communities of Mexico have a long tradition of consuming quelites. In this research, eight species of quelites that are traditionally consumed by indigenous communities of the Sierra Norte of Oaxaca, Mexico, were characterized: Eryngium foetidum L., Galinsoga parviflora Cav., Calceolaria mexicana Benth., Andinocleome magnifica (Briq.) Iltis & Cochrane, Cleoserrata speciosa (Raf.) H.H. Iltis, Phytolacca icosandra L., Cestrum nocturnum L. and Solanum nigrescens M.Martens & Galeotti. The ethnobotanical information of these species was recorded and the proximate composition, mineral content, and total phenolic and flavonoid content were determined. The antioxidant capacity of the samples was also investigated using ABTS (2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl), and ORAC (oxygen radical absorption capacity) methods. Quelites are available in the dry and rainy season. Quelites were found to have low energy contents while being good sources of fiber, of which A. magnifica possessed the highest concentration (8.61 ± 0.35 g/100 g fresh weight FW). Quelites were also found to provide essential minerals, with the primary contributions being potassium (4097.35 ± 12.28 mg/100 g FW) in C. mexicana, calcium (2418.63 ± 22.91 mg/100 g FW) in S. nigrescens, magnesium (1021.83 ± 10.58 mg/100 g FW) in E. foetidum, among others. C. speciosa and C. mexicana exhibited the highest concentration of phenols and flavonoids, which were found to be associated with higher antioxidant capacity. The quelites analyzed in this study are a potential source of accessible, nutritious, and healthy food, and can potentially help improve food security and health.

Modulation of gut microbiota by Mantequilla and Melipona honeys decrease low-grade inflammation caused by high fructose corn syrup or sucrose in rats.

Several studies have shown that consumption of honey is associated with various health benefits. However, there is scarce evidence on whether honeys modify the intestinal microbiota by preventing the inflammatory response in the host. Therefore, the aim of the present work was to study the effect of Melipona (Mel) and Mantequilla (Mtq) honeys, which contain different bioactive compounds and antioxidant capacity on gut microbiota and metabolic consequences in comparison with other sweeteners, in particular sucrose (S) and high fructose corn syrup (HFCS) in rats. The results of the present work showed that both honeys have polyphenols, flavonoids, antioxidant and bactericidal activities. Rats fed with both honeys gained less weight and body fat by increasing energy expenditure compared to S or HFCS and increased gene expression of antioxidant enzymes mediated by the transcription factor Nrf2. Analysis of the gut microbiota showed that consumption of both honeys modified the beta-diversity compared to those fed S or HFCS resulting in increased abundance of a specific cluster of bacteria of the Clostridium genus particularly Coprococcus eutactus, Defluviitalea saccharophila, Ruminicoccus gnavus and Ruminicoccus flavefaciens. As a result of the changes in the gut microbiota, there was a decrease in LPS- and TLR4-mediated low-grade inflammation and an increase in sIgA. Consumption of both honeys prevented glucose intolerance and increased adipocyte size compared to S or HFCS. In conclusion, consumption of MtqH or MelH can reduce metabolic endotoxemia by modifying the gut microbiota to prevent glucose intolerance.