Dietary regulation of the SIgA-gut microbiota interaction.

Gut microbiota (GM) is essential for host health, and changes in the GM are related to the development of various diseases. Recently, secretory immunoglobulin A (SIgA), the most abundant immunoglobulin isotype in the intestinal mucosa, has been found to play an essential role in controlling GM. SIgA dysfunction can lead to changes in the GM and is associated with the development of various GM-related diseases. Although in early stage, recent studies have shown that assorted dietary interventions, including vitamins, amino acids, fatty acids, polyphenols, oligo/polysaccharides, and probiotics, can influence the intestinal SIgA response and SIgA-GM interaction. Dietary intervention can enhance the SIgA response by directly regulating it (from top to bottom) or by regulating the GM structure or gene expression (from bottom to top). Furthermore, intensive studies involving the particular influence of dietary intervention on SIgA-binding to the GM and SIgA repertoire and the precise regulation of the SIgA response via dietary intervention are still exceedingly scarce and merit further consideration. This review summarizes the existing knowledge and (possible) mechanisms of the influence of dietary intervention on the SIgA-GM interaction. Key issues are considered, and the approaches in addressing these issues in future studies are also discussed.

Coconut oil and medium-chain fatty acids attenuate high-fat diet-induced obesity in mice through increased thermogenesis by activating brown adipose tissue.

Coconut oil (CO) and its main ingredients, medium-chain fatty acids (MCFA), present many benefits. Whether MCFA and CO play an equally valuable role in anti-obesity remains unclear. This study compared the anti-obesity effects of CO and MCFA [octanoic acid (C8:0) and decanoic acid (C10:0)] to gain insight into the underlying mechanism. Male C57BL/6J mice were fed either a low-fat diet (LFD) or high-fat diet (100% HFD) replaced with 2.5% MCFA (97.5% HFD + 2.5% MCFA) or 5% CO (95% HFD + 5% CO) for 17 weeks. CO and MCFA ameliorated the HFD-induced abnormal body and adipose depot weights, insulin sensitivity, and energy expenditure (EE), which was associated with brown adipose tissue (BAT) thermogenesis. Furthermore, CO enhanced the expression of thermogenesis markers in BAT, which was consistent with increased BAT activity. CO showed a better effect than MCFA in activating BAT to increase thermogenesis and energy metabolism to combat obesity, which may be attributed to the cooperation of MCFA and other substances in CO. This work provides evidence for the anti-obesity effects of CO, which could be a better alternative to lard in daily diet, rather than pure MCFA.

Cyanidin-3-O-glucoside Regulates the Expression of Ucp1 in Brown Adipose Tissue by Activating Prdm16 Gene.

(1) Background: Brown adipose tissue (BAT) burns energy to produce heat. Cyanidin-3-O-glucoside (C3G) can then enhance the thermogenic ability of BAT in vivo. However, the mechanism by which C3G regulates Ucp1 protein expression remains unclear. (2) Methods: In this study, C3H10T12 brown adipose cells and db/db mice and mice with high-fat, high-fructose, diet-induced obesity were used as the model to explore the effect of C3G on the expression of the Ucp1 gene. Furthermore, the 293T cell line was used for an in vitro cell transgene, a double luciferase reporting system, and yeast single hybridization to explore the mechanism of C3G in regulating Ucp1 protein. (3) Results: we identified that, under the influence of C3G, Prdm16 directly binds to the -500 to -150 bp promoter region of Ucp1 to activate its transcription and, thus, facilitate BAT programming. (4) Conclusions: This study clarified the mechanism by which C3G regulates the expression of the Ucp1 gene of brown fat to a certain extent.

Role of IgA in the early-life establishment of the gut microbiota and immunity: Implications for constructing a healthy start.

Colonization and maturation of the gut microbiota (GM) during early life is a landmark event that fundamentally influences the (early) immunity and later-life health of various mammals. This is a delicate, systematic process that is biologically actively regulated by infants and their mothers, where (secretory) IgA, an important regulator of microbes found in breast milk and generated actively by infants, may play a key role. By binding to microbes, IgA can inhibit or enhance their colonization, influence their gene expression, and regulate immune responses. IgA dysfunction during early life is associated with disrupted GM maturation and various microbe-related diseases, such as necrotizing enterocolitis and diarrhea, which can also have a lasting effect on GM and host health. This review discusses the process of early GM maturation and its interaction with immunity and the role of IgA (focusing on milk secretory IgA) in regulating this process. The possible application of this knowledge in promoting normal GM maturation processes and immune education has also been highlighted.

Gentisic acid prevents diet-induced obesity in mice by accelerating the thermogenesis of brown adipose tissue.

Since obesity occurs when energy intake is higher than energy expenditure, increasing energy expenditure is an effective strategy to prevent or treat obesity. Brown adipose tissue (BAT) is a classic energy-consuming organ whose thermogenesis function can be activated by dietary components. Gentisic acid (2,5-dihydroxybenzoic acid, (DHB)) is widely found in food and exhibits many physiological functions, which include anti-inflammatory, antimicrobial, antioxidant, and hepatoprotective properties. However, its anti-obesity effect and mechanism have yet to be examined. This study investigated the effect and mechanism of DHB in preventing diet-induced obesity in mice from the perspective of energy metabolism. The C57BL/6 mice were fed a normal diet (ND), a high-fat and high-fructose diet (HFFD) or HFFD plus 2 mg mL-1 DHB (DHB + HFFD) for 12 weeks. Measuring obesity, lipid metabolism, energy metabolism and BAT related indicators. Moreover, the C3H10T1/2 cells were used to assess the effect of DHB on brown adipocytes in vitro. The results proved that, at the end of the experiment, the body weight of the mice in the DHB + HFFD group was 14.97% lower than in the HFFD group. DHB reduced the weight of the major organs, improved insulin sensitivity, and decreased systemic lipid accumulation. Moreover, DHB administration significantly increased energy metabolism, which was (partly) due to the activation of BAT thermogenesis. Furthermore, DHB supplementation enhanced the expression of the fatty acid oxidation related proteins in BAT and the brown adipocytes, indicating that DHB augmented the utilization of fatty acids by BAT, which is the primary substance of thermogenesis. This study reveals that DHB administration prevents HFFD induced obesity in mice by (at least partly) accelerating the oxidation of fatty acids and stimulating the thermogenesis of BAT.

Interaction between IgA and gut microbiota and its role in controlling metabolic syndrome.

Immunoglobulin A (IgA) is the most abundant immunoglobulin isotype secreted into the mucosal tissues, mainly intestinal mucus. Humans can produce several grams of IgA every day, accounting for three quarters of the body's total immunoglobulin content. IgA, together with mucus and antimicrobial peptides, forms the first line of defence for intestinal epithelial cells, protecting them from a significant number of intestinal antigens. IgA also plays a principal role in controlling the gut microbiota (GM), and disruption in IgA can result in dysbiosis, such as the enrichment of Proteobacteria, which are generally bound by IgA. Proteobacteria overexpansion is also usually seen in obesity and colitis. Consistent with this, IgA dysfunction frequently results in metabolic syndrome (MetS), including conditions such as obesity, adiposity, insulin resistance, and inflammation. In contrast, enhanced IgA function can improve, and even prevent, MetS. Interactions among IgA, GM, and metabolism provide a promising avenue to combat MetS.

The influence of oxygen on the metabolites of phenolic blueberry extract and the mouse microflora during in vitro fermentation.

The elevated intestinal oxygen in certain unhealthy conditions (e.g., mucosa injury) enhances the expansion of aerobic/facultative anaerobic bacteria (mainly Proteobacteria) in gut microbiota (GM) and is strongly linked to various diseases. The alteration of GM, influenced by oxygen, may affect the bioavailability of dietary polyphenols. In vitro digestion, dialysis and fermentation of phenolic blueberry extract (BE) were performed here using the GM of mice under different oxygen conditions. Oxygen delayed the degradation of the main phenolic components, including quercetin, kaempferol and their rutinose-conjugates, in BE during in vitro fermentation. In addition, the metabolites of BE were also influenced by oxygen. Oxygen skewed the production of 3-hydroxyphenylacetatic acid to 4-hydroxyphenylacetatic acid. Moreover, oxygen also blunted hippuric, 3-phenylpropionic, and 3-hydroxycinnamic acids production. Furthermore, oxygen enhanced the expansion of Salmonella and Escherichia belonging to phylum Proteobacteria and suppressed the proliferation of the anaerobic bacteria Clostridium and Bacteroides belonging to phyla Firmicutes and Bacteroidetes, respectively, which was reversed by BE supplementation.

Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet-Fed Mice through Increased Thermogenesis.

BACKGROUND: Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. OBJECTIVES: In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)-fed obese mice. METHODS: The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. RESULTS: After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. CONCLUSIONS: Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

p-Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1-RPS6.

Brown adipose tissue (BAT) has long been recognized as an energy-consuming organ and a possible target for combating metabolism disorder. Although numerous studies have demonstrated the ability of phytochemical phenolic acids to improve obesity by activating BAT, the underlying mechanism or mechanism therein remain obscure. In this study, diet-induced obese mice, genetically obese mice, and C3H10T1/2 cells were used to examine the effects of p-Coumaric acid (CA) on metabolism profiles. The results showed that CA prevented metabolic syndromes in the two mice models through the activation of BAT. This phenomenon was closely linked to the upregulation of uncoupling protein 1 (UCP1) and the accelerated burning of fatty acids and glucose, which consequently enhanced the energy expenditure and thermogenesis. Similar results were also obtained in vitro. Importantly, these effects were mediated by the mammalian target of rapamycin complex 1 (mTORC1)-RPS6 pathway. These findings reveal, to the best of our knowledge for the first time, the close correlation between mTORC1-RPS6 and BAT-mediated thermogenesis, and, in addition, the key role played by mTORC1-RPS6 in mediating phenolic acids-induced activation of BAT, thus preventing obesity.

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid.

SCOPE: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). METHODS AND RESULTS: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TßMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. CONCLUSION: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Chlorogenic Acid Stimulates the Thermogenesis of Brown Adipocytes by Promoting the Uptake of Glucose and the Function of Mitochondria.

Brown adipose tissue (BAT) prevents obesity and related diseases by uncoupling oxidative phosphorylation with adenosine triphosphate. Previous studies have demonstrated that polyphenols can promote the thermogenesis of BAT in mice. Chlorogenic acid (CGA) is a common phenolic acid found in fruits and vegetables, as well as traditional Chinese medicine, which is responsible for a variety of physiological activities. However, it is still unclear whether CGA has positive effects on the thermogenesis of BAT. In this study, CGA enhances the thermogenesis and proton leak of brown adipocytes, however, no changes are evident regarding the differentiation of C3 H10 T1/2 into brown adipocytes. Surprisingly, CGA promotes the uptake of glucose by upregulating the glucose transporter 2 and phosphofructokinase. Moreover, CGA increases the number and the function of mitochondrial. Taken together, CGA stimulates thermogenesis of brown adipocytes by promoting the uptake of glucose and the function of mitochondria. PRACTICAL APPLICATION: Chlorogenic acid (CGA) is widely found in fruits, vegetables, and traditional Chinese medicines, which has been considered to have antibacterial and anti-inflammatory function. However, whether it has the function of resisting obesity and promoting thermogenesis is still unclear. In this study, brown adipocyte was used to explore the function and mechanism of CGA on thermogenesis. It provides new ideas for the utilization of foods rich in CGA and traditional Chinese medicine.

Blueberry Extract Improves Obesity through Regulation of the Gut Microbiota and Bile Acids via Pathways Involving FXR and TGR5.

The metabolic improvement effect of blueberries has long been recognized, although its precise mechanism(s) remains obscure. Here, we show that phenolic blueberry extract (BE) treatment improved diet- and genetically induced metabolic syndromes, which were linked to increased energy expenditure in brown adipose tissue (BAT) and improved lipid metabolism in the liver via pathways involving the bile acid (BA) receptors TGR5 and FXR. These observations were strongly correlated with the regulation of BAs (e.g., a decrease in the FXR inhibitors TαMCA and TßMCA) and the gut microbiota (GM) (e.g., an expansion of Bifidobacteria and Lactobacillus), because antibiotic treatment completely blunted the regulation of the GM and BAs and the metabolic effects of BE. We also observed similar results in db/db mice. Furthermore, treating mouse primary cells derived from the liver and BAT with the combinations of BAs mimicking the in vivo alterations upon BE treatment mirrored the in vivo observations in mice.

Vanillin Alleviates High Fat Diet-Induced Obesity and Improves the Gut Microbiota Composition.

Vanillin, a simple phenolic compound, exists marginally in some plants and can be produced by microbes. This study uses high-fat-diet (HFD) induced obese mice to study the effect of vanillin on obesity and obtain positive results. First, both body and adipose tissue weight are reduced. Second, the blood properties signaling certain disorders such as ALT, LDH, glucose, cholesterol, LDL-C, TG and HDL-C are ameliorated and both insulin sensitivity, and glucose tolerance are improved. Third, vanillin reduced elevated levels of inflammatory factors including LPS, IL-6, and TNF-α in plasma and liver tissue resulting from obesity. Finally, the production of short chain fatty acids (SCFAs) is enhanced. Additionally, study results demonstrate that vanillin significantly alleviates obesity-related gut microbiota (GM) disorders including the decrease of alpha- and beta-diversity. Furthermore, vanillin reduces the abundance of Firmicutes phylum, increases the richness of Bacteroidetes and Verrucomicrobiota phyla, and inhibits the expansion of the lipopolysaccharide (LPS)-producing bacteria Bilophila genus and the H2S-producing bacteria Desulfovibrio genus.

A fast and accurate way to determine short chain fatty acids in mouse feces based on GC-MS.

Short-chain fatty acids (SCFAs) in the gut are mainly produced by the anaerobic microbial fermentation of unabsorbed dietary carbohydrates in the large bowel. Quantitative determinations of SCFAs in feces and colonic contents are necessary when studying the impact of fiber-rich food (such as fruits and vegetables) on health. We made the following crucial improvements to the method currently widely used: optimized the lyophilization period from 12 h to 3.5 h; disposed of the procedure for precise weight control; lowered the extraction temperature from 25 °C to 4 °C; shortened the extraction time from 45 min to 15 min; and significantly improved the extraction efficiency of acetic acid, propionic acid and butyric acid by 12.91%, 19.95% and 13.08%, respectively. Furthermore, to evaluate the applicability of this novel approach, we applied our method to determine the SCFAs in the feces and colonic contents of mice fed on different diets, and observed distinct results.

Vanillic acid activates thermogenesis in brown and white adipose tissue.

Anthocyanins have a positive effect on resistant obesity; however they cannot usually be absorbed directly but, instead, are metabolized by gut microbiota. This study will examine the effects and the mechanism of vanillic acid on the prevention of obesity induced by diet, which is one of the anthocyanin metabolites. We fed C57BL/6J mice vanillic acid supplements in a high fat and high fructose diet for 16 weeks. Body weight, fat pat weight, and food and water intake were monitored. Glucose homeostasis was assessed with a glucose or insulin tolerance test. The sizes of adipose cells and lipid droplets were analyzed by histology staining, while the expression of genes and proteins was analyzed by quantitative real-time PCR, western blot and tissue-blot immunoassay. The results demonstrated that vanillic acid contributed to the reduction of body weight gain, improved glucose tolerance and insulin resistance, and maintained body temperature. Furthermore, vanillic acid was found to promote thermogenesis and mitochondrial synthesis of brown adipose tissue and inguinal white adipose tissue. This study demonstrated that vanillic acid could prevent obesity by activating BAT thermogenesis and the promotion of inguinal WAT browning.

Influence of Tannin Extract and Yeast Extract on Color Preservation and Anthocyanin Content of Mulberry Wine.

The color of mulberry wine is extremely unstable in processing and aging. This paper investigates the effects of tannin extract and yeast extract on the color and color-preserving characteristics of mulberry wine made from the Dashi cultivar. The results showed that the maximum absorption wavelength in both tannin extract and yeast extract groups changed generating the red shift effect. The color of the tannin extract maintained a good gloss in the first 4 months, while the yeast extract group showed remarkable color preservation for the first 3 months. The total anthocyanin and cyanidin-3-rutinoside contents in both experiment groups were significantly higher than that of the control group, thus proving that tannin extract and yeast extract both exert a remarkably positive effect on preserving the color of mulberry wine during its aging. Moreover, sensory analysis indicated that the quality of mulberry wine treated with tannin extract was significantly higher than that of the control. PRACTICAL APPLICATION: The distinct color of mulberry wine is one of the foremost qualities that imprints on consumers' senses, but it is extremely unstable in processing and aging. However, the color protection of mulberry wine was not studied previously. In this study, we found that tannin extract and yeast extract both exert a remarkably positive effect on preserving the color of mulberry wine during aging. The study is of great significance as a guide to improving the color stability of mulberry wine, thereby also improving and promoting the development of the mulberry deep processing industry.

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function.

SCOPE: Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. METHODS AND RESULTS: Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. CONCLUSION: Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.