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.

Amino Acid Catabolism: An Overlooked Area of Metabolism.

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.

Genistein-mediated thermogenesis and white-to-beige adipocyte differentiation involve transcriptional activation of cAMP response elements in the Ucp1 promoter.

Genistein is an isoflavone present in soybeans and is considered a bioactive compound due to its widely reported biological activity. We have previously shown that intraperitoneal genistein administration and diet supplementation activates the thermogenic program in rats and mice subcutaneous white adipose tissue (scWAT) under multiple environmental cues, including cold exposure and high-fat diet feeding. However, the mechanistic insights of this process were not previously unveiled.

Chaya (Cnidoscolus aconitifolius (Mill.) I.M. Johnst) leaf extracts regulate mitochondrial bioenergetics and fatty acid oxidation in C2C12 myotubes and primary hepatocytes.

Ethnopharmacological Relevance: Chaya (Cnidoscolus aconitifolius (Mill.) I.M.

Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.

Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation.

PPARα/RXRα downregulates amino acid catabolism in the liver via interaction with HNF4α promoting its proteasomal degradation.

The preservation of body proteins is essential to guarantee their functions in organisms. Therefore, the utilization of amino acids as energy substrates is regulated by a precise fine-tuned mechanism. Recent evidence suggests that the transcription factors peroxisome proliferator-activated receptor alpha (PPARα) and hepatocyte nuclear factor 4 alpha (HNF4α) are involved in this regulatory mechanism.

ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet.

Carbohydrate responsive element-binding protein (ChREBP) has been identified as a primary transcription factor that maintains energy homeostasis through transcriptional regulation of glycolytic, lipogenic, and gluconeogenic enzymes in response to a high-carbohydrate diet. Amino acids are important substrates for gluconeogenesis, but nevertheless, knowledge is lacking about whether this transcription factor regulates genes involved in the transport or use of these metabolites. Here, we demonstrate that ChREBP represses the expression of the amino acid transporter sodium-coupled neutral amino acid transporter 2 (SNAT2) in response to a high-sucrose diet in rats by binding to a carbohydrate response element (ChoRE) site located -160 bp upstream of the transcriptional start site in the SNAT2 promoter region.

Angiotensin-(1-7) induces beige fat thermogenesis through the Mas receptor.

Objective: Angiotensin-(1-7) [Ang-(1-7)], a component of the renin angiotensin system, is a vasodilator that exerts its effects primarily through the Mas receptor. The discovery of the Mas receptor in white adipose tissue (WAT) suggests an additional role for this peptide. The aim of the present study was to assess whether Ang-(1-7) can induce the expression of thermogenic genes in white adipose tissue and increase mitochondrial respiration in adipocytes.

PPARα via HNF4α regulates the expression of genes encoding hepatic amino acid catabolizing enzymes to maintain metabolic homeostasis.

The liver is the main organ involved in the metabolism of amino acids (AA), which are oxidized by amino acid catabolizing enzymes (AACE). Peroxisome proliferator-activated receptor-α (PPARα) stimulates fatty acid β-oxidation, and there is evidence that it can modulate hepatic AA oxidation during the transition of energy fuels. To understand the role and mechanism of PPARα's regulation of AA catabolism, the metabolic and molecular adaptations of Ppara-null mice were studied.