Targeted delivery of nutraceuticals derived from food for the treatment of obesity and its related complications.

Nutraceuticals which are abundant in foods have attracted much attention due to their bioactive activities of anti-obesity, anti-hyperlipidemia and anti-atherosclerosis. Unfortunately, the poor bioavailability severely undermines their envisioned benefits. Therefore, there is an urgent need to develop suitable delivery systems to promote the benefits of their biological activity. Targeted drug delivery system (TDDS) is a novel drug delivery system that can selectively concentrate drugs on targets in the body, improve the bioavailability of agents and reduce side effects. This emerging drug delivery system provides a new strategy for the treatment of obesity with nutraceuticals and would be a promising alternative to be widely used in the food field. This review summarizes the recent studies on the application in the targeted delivery of nutraceuticals for treating obesity and its related complications, especially the available receptors and their corresponding ligands for TDDS and the evaluation methods of the targeting ability.

Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPARγ signaling activation.

BACKGROUND: Ulcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms. RESULTS: Using 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in the enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions. CONCLUSIONS: Overall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite. Video Abstract.

Dietary Luffa cylindrica (L.) Roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice.

High circulating branched-chain amino acid (BCAA) levels can be diagnosis indicators for obesity. Luffa cylindrica (luffa) is one of vegetables against obesity. However, whether the anti-obesity of luffa is associated with BCAA metabolism and gut microbiota remains unknown. Here, we used conventionally raised diet-induced obese (DIO) mice to prove dietary luffa could reduce higher circulating BCAA levels and upregulate the tissue-specific expressions of BCAA-catabolizing enzymes. Meanwhile, dietary luffa selectively decreased the relative abundances of g_Enterortabdus, g_Eubacterium_xylanophilum_group and g_Butyricicoccus that exhibited significantly positive correlations with BCAA levels, BMI and HOMA-IR. Bacterial functionality prediction indicated dietary luffa potentially inhibited bacterial BCAA biosynthesis for reducing BCAAs supplementation. More importantly, dietary luffa had no impacts on BCAA catabolism in germ-free-mimic DIO mice. Thus, dietary luffa improved BCAA dysfunction via gut microbiota to attenuate obesity. This study offers a novel insight into dietary intervention against obesity from the aspect of gut microbiota-amino acid metabolism.

The modulation of Luffa cylindrica (L.) Roem supplementation on gene expression and amino acid profiles in liver for alleviating hepatic steatosis via gut microbiota in high-fat diet-fed mice: insight from hepatic transcriptome analysis.

Luffa cylindrica is a nutrient-dense vegetable with medical properties and can alleviate metabolic diseases. Numerous evidences demonstrated gut microbiota impacted the progress of nonalcoholic fatty liver disease (NAFLD). This study was to investigate the underlying mechanism of L. cylindrica supplementation against NALFD via gut microbiota from hepatic transcriptional and metabolic analysis. In diet-induced obese mice, we observed L. cylindrica supplementation (2 g/kg body weight) effectively alleviated high-fat diet-induced obese symptoms such as body weight, fat deposition, and insulin resistance. Notably, L. cylindrica supplementation significantly relieved hepatic steatosis and inflammation infiltration to decrease hepatic toxicity. RNA-sequencing analysis showed that 130 hepatic genes in total significantly altered responding to L. cylindrica supplementation. And signaling pathway analysis revealed that L. cylindrica supplementation down-regulated the transcriptional expressions of CD36 and Rxrg to inhibit hepatic lipid synthesis. Moreover, L. cylindrica supplementation increased the transcriptional expressions of Ass1, Cps1, Cth, Got1, Tat, and Gls2 to enhance amino acid levels (Gly, Ala, Pro, Val, Ile, Asn, Met, and Phe) and improve hepatic abnormal gluconeogenesis. Furthermore, in antibiotic-treated obese mice, L. cylindrica supplementation did not change these gene expressions along with the hepatic levels of lipid and amino acids. Taken together, L. cylindrica supplementation could effectively suppress hepatic steatosis in diet-induced obese mice through inhibiting lipid synthesis and enhancing amino acid levels in liver, which depended on gut microbiota. Thus, L. cylindrica might be one promising dietary supplementation targeting at gut microbiota to reduce NAFLD risk.

Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.

The gut microbiota, identified as the target for vegetables, can affect the development of obesity and associated metabolic syndromes. As a medicinal and edible plant, Luffa cylindrica (L.) Roem (LC) has abundant nutrients that can effectively reduce obesity risk. However, the interaction between the prevention effects of LC against obesity and the modulating gut microbiota of LC remain obscure. This study demonstrated LC supplementation improved high-fat diet (HFD)-induced gut microbiota dysbiosis and significantly enhanced short-chain fatty acid (SCFA)-producing bacteria (e.g., Blautia) along with SCFA content accumulation in the gut. Meanwhile, LC supplementation substantially restored gut barrier damage in long-term HFD treatment. Moreover, LC supplementation improved HFD-induced overweight, hyperlipidemia, insulin resistance, and chronic inflammation. Gene expression profiles showed that LC displayed an important impact on hepatic lipid transport and lipid synthesis (sterol regulatory element binding transcriptional factor 1c-peroxisome proliferator-activated receptor γ signaling pathway). More importantly, an antibiotic treatment experiment demonstrated that the beneficial effects of LC in reducing obesity risk largely depended on the gut microbiota, especially SCFA-producing bacteria (e.g., Blautia). Therefore, LC supplementation improved gut microbiota dysbiosis via enhancing SCFA-producing bacteria (e.g., Blautia), maintained gut barrier integrity, and alleviated the development of obesity. Overall, LC would provide a potential dietary intervention strategy against obesity and enteral homeostasis dysbiosis through modulating the gut microbiota.-Zhang, L., Shi, M., Ji, J., Hu, X., Chen, F. Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.