Journal of Nutritional Biochemistry最新文献

Nonalcoholic fatty liver disease (NAFLD) is reaching pandemic proportions due to overnutrition. The understanding of advanced stages that recapitulate the human pathology is of great importance to get a better mechanistic insight. We hypothesized that feeding of WT (C57BL) mice with a diet containing a high content of fat (21%), sugar (41.5%) and 1.25% of cholesterol (called from now on high fat, sucrose and cholesterol diet, HFSCD) will reproduce the characteristics of disease severity. Analysis of 16 weeks HFSCD-fed mice demonstrated increased liver weight and plasmatic liver damage markers compared with control diet (CD)-fed mice. HFSCD-fed mice developed greater hepatic triglyceride, cholesterol and NEFA content, inflammation and NAFLD activity score (NAS) indicating an advanced disease. HFSCD-fed mice displayed augmented hepatic total CD3+ T and Th9 lymphocytes, as well as reduced Th2 lymphocytes and CD206 anti-inflammatory macrophages. Moreover, T cells and anti-inflammatory macrophages correlated positively and inversely, respectively, with intrahepatic cholesterol content. Consistently, circulating cytotoxic CD8+ T lymphocytes, Th1, and B cell levels were elevated in HFSCD-fed WT mice. Hepatic and adipose tissue expression analysis demonstrated changes in fibrotic and metabolic genes related with cholesterol, triglycerides, and fatty acid synthesis in HFSCD-fed WT. These mice also exhibited reduced antioxidant capacity and autophagy and elevated ERK signaling pathway activation and CHOP levels. Our results indicate that the feeding with a cholesterol-enriched diet in WT mice produces an advanced NAFLD stage with fibrosis, characterized by deficient autophagy and ER stress along with inflammasome activation partially via ERK pathway activation.

Previously, we demonstrated that caloric restriction (CR) stimulates the synthesis, conjugation, secretion, and deconjugation of taurine and bile acids in the intestine, as well as their reuptake. Given taurine's potent antiobesogenic properties, this study aimed to assess whether the CR-induced shift in taurine homeostasis contributes to adipose tissue loss. To verify that, male C57Bl/6 mice were subjected to 20% CR or ad libitum feeding, with variations in cage bedding and gut microbiota conditions. Additional groups received taurine supplementation or were fed a low-taurine diet (LTD). The results showed that in CR animals, taurine derived from the intestine was preferentially trafficked to epididymal white adipose tissue (eWAT) over other tested organs. Besides increased levels of taurine transporter TauT, gene expression of Cysteine dioxygenase (Cdo) involved in taurine synthesis was upregulated in CR eWAT. Taurine concentration in adipocytes was inversely correlated with fat pad weight of CR mice. Different types of cage bedding did not impact eWAT taurine levels; however, the lack of bedding and consumption of a diet high in soluble fiber did. Depleting gut microbiota with antibiotics or inhibiting bile salt hydrolase (BSH) activity reduced WAT taurine concentration in CR mice. Taurine supplementation increased taurine levels in WAT and brown adipose tissue (BAT), promoting fat loss in CR animals. LTD consumption blunted WAT loss in CR animals, with negligible impact on BAT. This study provides multiple insights into taurine's role in CR-triggered fat loss and describes a novel communication path between the liver, gut, microbiota, and WAT, with taurine acting as a messenger.

Nonalcoholic fatty liver disease (NAFLD) constitutes one of major worldwide health problem which typically progressively results in nonalcoholic steatohepatitis (NASH) and eventually cirrhosis and liver cancer. Liver-specific deletion of INSIG1 promotes SREBP1 nuclear translocation to activate downstream lipogenic genes expression, leading to lipid accumulation. However, the underlying pathogenesis of NAFLD, and particularly involved in miRNA participation are still to be thoroughly explored. Here, we found that miR-363-3p was significantly overexpressed in high-fat, high-cholesterol (HFHC) diet mice liver tissue and fatty acid-induced steatosis cells. miR-363-3p directly targets INSIG1 to inhibit its expression, thereby facilitating the cleavage of SREBP and nuclear translocation to activate subsequent transcription of lipogenic genes in vitro and in vivo. In addition, we identified apigenin, a natural flavonoid compound, inhibited miR-363-3p expression to up-regulate INSIG1 and suppress nuclear translocation of SREBP1, thereby down-regulated lipogenic genes expression in steatosis cells and HFHC diet mice liver tissues. Taken together, our results demonstrated that miR-363-3p as a key regulator of hepatic lipid homeostasis targeted INSIG1, and apigenin alleviated NAFLD through the miR-363-3p/INSIG1/SREBP1 pathway. This indicates that reduction of miR-363-3p levels as a possible treatment of hepatic steatosis and provides a potential new therapeutic strategy for targeting miRNA to ameliorate NAFLD.

This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 μg/kg BW of LPS. At 4 h postchallenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P<.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.

Nonsoy legumes offer many health benefits, including improved arterial function, reduced cholesterol levels, and better management of cardiovascular diseases and type 2 diabetes. This systematic review and meta-analysis aim to clarify the inconclusive findings from randomized controlled trials (RCTs) by comprehensively evaluating the effects of nonsoy legumes consumption on serum levels of inflammatory biomarkers and Adiponectin. The search encompassed databases up to January 2024, including PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL to retrieve all RCTs examining the effects of nonsoy legumes on inflammatory biomarkers or Adiponectin. The effect sizes quantified as mean differences (MD) and standard deviations (SD) of outcomes, and an overall effect estimate was derived using a random-effects model. RCTs examining serum levels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1β (IL-1β), and Adiponectin were included in the final meta-analysis. Results revealed that consumption of nonsoy legumes increased Adiponectin serum levels (P=.0017) and reduced IL-1β serum levels (P<.0001). However, it may not significantly affect CRP (P=.2951), IL-6 (P=.2286), and TNF-α (P=.6661) levels. Subgroup analyses showed that nonsoy legumes consumption significantly decreased TNF-α serum levels in studies involving healthy participants. Additionally, sensitivity analysis using the leave-one-out method suggested a potential significant reduction in serum levels of IL-6. This study indicates that consuming nonsoy legumes can increase levels of Adiponectin and decrease serum levels of IL-1β in overweight or obese adults.

The prevalence of type 2 diabetes is increasing worldwide. Various molecular mechanisms have been proposed to interfere with the insulin signaling pathway. Recent advances in proteomics and genomics indicate that one such mechanism involves the post-transcriptional regulation of insulin signaling by microRNA (miRNA). These noncoding RNAs typically induce messenger RNA (mRNA) degradation or translational repression by interacting with the 3′ untranslated region (3′UTR) of target mRNA. Dietary components and patterns, which can either enhance or impair the insulin signaling pathway, have been found to regulate miRNA expression in both in vitro and in vivo studies. This review provides an overview of the current knowledge of how dietary components influence the expression of miRNAs related to the control of the insulin signaling pathway and discusses the potential application of these findings in precision nutrition.

Nobiletin has been reported to protect against obesity-related metabolic disorders by enhancing the circadian rhythm; however its effects on lipid metabolism in adipose tissue are unclear. In this study, mice were fed with high-fat diet (HFD) for four weeks firstly and gavaged with 50 or 200 mg/kg bodyweight/day nobiletin at Zeitgeber time (ZT) 4 for another four weeks while still receiving HFD. At the end of the 8-week experimental period, the mice were sacrificed at ZT4 or ZT8 on the same day. Mature 3T3-L1 adipocytes were treated with nobiletin in the presence or absence of siBmal1, siRora, siRorc, SR8278 or SR9009. Nobiletin reduced the weight of white adipose tissue (WAT) and the size of adipocytes in WAT. At ZT4, nobiletin decreased the TG, TC and LDL-c levels and increased serum FFA level and glucose tolerance. Nobiletin triggered the lipolysis of mesenteric and epididymal WAT at both ZT4 and ZT16. Nobiletin increased the level of RORγ at ZT16, that of BMAL1 and PPARγ at ZT4, and that of ATGL at both ZT4 and ZT16. Nobiletin increased lipolysis and ATGL levels in 3T3-L1 adipocytes in Bmal1- or Rora/c- dependent manner. Dual luciferase assay indicated that nobiletin enhanced the transcriptional activation of RORα/γ on Atgl promoter and decreased the repression of RORα/γ on PPARγ-binding PPRE. Promoter deletion analysis indicated that nobiletin inhibited the suppression of PPARγ-mediated Atgl transcription by RORα/γ. Taken together, nobiletin elevated lipolysis in WAT by increasing ATGL levels through activating the transcriptional activity of RORα/γ and decreasing the repression of RORα/γ on PPARγ-binding PPRE.

Methylmercury (MeHg) is a ubiquitous environmental contaminant, well known for its neurotoxic effects. MeHg can interact with several nutrients in the diet and affect nutrient metabolism, however the interaction between MeHg and dietary proteins has not been thoroughly investigated. Male BALB/c mice were fed diets based on either casein, cod or chicken as protein sources, which were or were not spiked with MeHg (3.5 mg Hg kg⁻¹). Following 13 weeks of dietary exposure to MeHg, the animals accumulated mercury in a varying degree depending on the diet, where the levels of mercury were highest in the mice fed casein and MeHg, lower in mice fed cod and MeHg, and lowest in mice fed chicken and MeHg in all tissues assessed. Assessment of gut microbiota revealed differences in microbiota composition based on the different protein sources. However, the introduction of MeHg eliminated this difference. Proteomic profiling of liver tissue uncovered the influence of the dietary protein sources on a range of enzymes related to Phase I and Phase II detoxification mechanisms, suggesting an impact of the diet on MeHg metabolism and excretion. Also, enzymes linked to pathways including methionine and glycine betaine cycling, which in turn impact the production of glutathione, an important MeHg conjugation molecule, were up-regulated in mice fed chicken as dietary protein. Our findings indicate that dietary proteins can affect expression of hepatic enzymes that potentially influence MeHg metabolism and excretion, highlighting the relevance of considering the dietary composition in risk assessment of MeHg through dietary exposure.