Search

Background/Objective: In recent studies, it has been shown that dietary bioactive compounds can produce health benefits; however, it is not known whether an improvement in solubility can enhance their biological effects. Thus, the aim of this work was to study whether co-amorphous (CoA) naringenin or fisetin with enhanced solubility modify glucose and lipid metabolism, thermogenic capacity and gut microbiota in mice fed a high-fat, high-sucrose (HFSD) diet. Methods: Mice were fed with an HFSD with or without CoA-naringenin or CoA-fisetin for 3 months. Body weight, food intake, body composition, glucose tolerance, hepatic lipid composition and gut microbiota were assessed. Results: CoA-naringenin demonstrated significant reductions in fat-mass gain, improved cholesterol metabolism, and enhanced glucose tolerance. Mice treated with CoA-naringenin gained 45% less fat mass and exhibited improved hepatic lipid profiles, with significant reductions seen in liver triglycerides and cholesterol. Additionally, both CoA-flavonoids increased oxygen consumption (VO2), contributing to enhanced energy expenditure and improved metabolic flexibility. Thermogenic activation, indicated by increased UCP1 and PGC-1α levels, was observed with CoA-fisetin, supporting its role in fat oxidation and adipocyte size reduction. Further, both CoA-flavonoids modulated gut microbiota, restoring diversity and promoting beneficial bacteria, such as Akkermansia muciniphila, which has been linked to improved metabolic health. Conclusions: These findings suggest that co-amorphous naringenin or fisetin offers promising applications in improving solubility, metabolic health, and thermogenesis, highlighting the potential of both as therapeutic agents against obesity and related disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length. Their main function is to regulate gene expression at the posttranscriptional level by inhibiting the translation of messenger RNAs (mRNAs). miRNAs originate in the cell nucleus from specific genes, where they can perform their function. However, they can also be found in serum, plasma, or other body fluids travelling within vesicles called exosomes and/or bound to proteins or other particles such as lipoproteins. miRNAs can form complexes outside the cell where they are synthesized, mediating paracrine and endocrine communication between different tissues. In this way, they can modulate the gene expression and function of distal cells. It is known that the expression of miRNAs can be affected by multiple factors, such as the nutritional or pathological state of the individual, or even in conditions such as obesity, insulin resistance, or after any dietary intervention. In this review, we will analyse miRNAs whose expression and circulation are affected in conditions of obesity and insulin resistance, as well as the changes generated after a dietary intervention, with the purpose of identifying new possible biomarkers of early response to nutritional treatment in these conditions. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake. [ABSTRACT FROM AUTHOR]

The human gut is home to a complex array of microorganisms interacting with the host and each other, forming a community known as the microbiome. This community has been linked to human health and disease, but understanding the underlying interactions is still challenging for researchers. Standard studies typically use high-throughput sequencing to analyze microbiome distribution in patient samples. Recent advancements in meta-omic data analysis have enabled computational modeling strategies to integrate this information into an in silico model. However, there is a need for improved parameter fitting and data integration features in microbial community modeling. This study proposes a novel alternative strategy utilizing state-of-the-art dynamic flux balance analysis (dFBA) to provide a simple protocol enabling accurate replication of abundance data composition through dynamic parameter estimation and integration of metagenomic data. We used a recurrent optimization algorithm to replicate community distributions from three different sources: mock, in vitro, and clinical microbiome. Our results show an accuracy of 98% and 96% when using in vitro and clinical bacterial abundance distributions, respectively. The proposed modeling scheme allowed us to observe the evolution of metabolites. It could provide a deeper understanding of metabolic interactions while taking advantage of the high contextualization features of GEM schemes to fit the study case. The proposed modeling scheme could improve the approach in cases where external factors determine specific bacterial distributions, such as drug intake. [ABSTRACT FROM AUTHOR]

Amino acids have been extensively studied in nutrition, mainly as key elements for maintaining optimal protein synthesis in the body as well as precursors of various nitrogen-containing compounds. However, it is now known that amino acid catabolism is an important element for the metabolic control of different biological processes, although it is still a developing field to have a deeper understanding of its biological implications. The mechanisms involved in the regulation of amino acid catabolism now include the contribution of the gut microbiota to amino acid oxidation and metabolite generation in the intestine, the molecular mechanisms of transcriptional control, and the participation of specific miRNAs involved in the regulation of amino acid degrading enzymes. In addition, molecules derived from amino acid catabolism play a role in metabolism as they are used in the epigenetic regulation of many genes. Thus, this review aims to examine the mechanisms of amino acid catabolism and to support the idea that this process is associated with the immune response, abnormalities during obesity, in particular insulin resistance, and the regulation of thermogenesis. [ABSTRACT FROM AUTHOR]