Lacticaseibacillus rhamnosus HF01 fermented yogurt alleviated high-fat diet-induced obesity and hepatic steatosis via the gut microbiota-butyric acid-hepatic lipid metabolism axis.

The objective of this study was to investigate the anti-obesity effects and underlying mechanism of Lacticaseibacillus rhamnosus HF01 fermented yogurt (HF01-Y). Herein, obesity was induced in mice through a high-fat diet and the changes in the gut microbiota were evaluated using 16S rRNA gene sequencing, combined with the expression levels of the liver AMPK signaling pathway to analyze the potential relationship between HF01-Y-mediated gut microbiota and obesity. The results showed that supplementation with HF01-Y improved obesity-related phenotypes in mice, including reduced body weight, improved serum lipid profiles, and decreased hepatic lipid droplet formation. In addition, HF01-Y altered the composition of the gut microbiota in obese mice, significantly upregulated norank_f__Muribaculaceae, unclassified_c__Clostridia, Blautia, unclassified_o__Bacteroidales, and Rikenellaceae_RC9_gut_group, while downregulating unclassified_f__Desulfovibrionaceae, Colidextribacter, and unclassified_f__Oscillospiraceae. These alterations led to an increase of the cecum butyric acid content, which in turn indirectly promoted the activation of the AMPK signaling pathway, subsequently, inhibited fat synthesis, and promoted fatty acid oxidation related gene expression. Therefore, HF01-Y was likely to alleviate hepatic fat and relieve obesity by modulating the gut microbiota-butyric acid-hepatic lipid metabolism axis, ultimately promoting host health.

A Metabolomics Study of the Effects of Eleutheroside B on Glucose and Lipid Metabolism in a Zebrafish Diabetes Model.

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 µg∙mL-1) and EB (50, 100, and 150 µg∙mL-1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism.

Mulberry branch fiber improved lipid metabolism and egg yolk fatty acid composition of laying hens via the enterohepatic axis.

BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.

Toosendanin induces hepatotoxicity via disrupting LXRα/Lipin1/SREBP1 mediated lipid metabolism.

Toosendanin (TSN) is the main active compound derived from Melia toosendan Sieb et Zucc with various bioactivities. However, liver injury was observed in TSN limiting its clinical application. Lipid metabolism plays a crucial role in maintaining cellular homeostasis, and its disruption is also essential in TSN-induced hepatotoxicity. This study explored the hepatotoxicity caused by TSN in vitro and in vivo. The lipid droplets were significantly decreased, accompanied by a decrease in fatty acid transporter CD36 and crucial enzymes in the lipogenesis including ACC and FAS after the treatment of TSN. It was suggested that TSN caused lipid metabolism disorder in hepatocytes. TOFA, an allosteric inhibitor of ACC, could partially restore cell survival via blocking malonyl-CoA accumulation. Notably, TSN downregulated the LXRα/Lipin1/SREBP1 signaling pathway. LXRα activation improved cell survival and intracellular neutral lipid levels, while SREBP1 inhibition aggravated the cell damage and caused a further decline in lipid levels. Male Balb/c mice were treated with TSN (5, 10, 20 mg/kg/d) for 7 days. TSN exposure led to serum lipid levels aberrantly decreased. Moreover, the western blotting results showed that LXRα/Lipin1/SREBP1 inhibition contributed to TSN-induced liver injury. In conclusion, TSN caused lipid metabolism disorder in liver via inhibiting LXRα/Lipin1/SREBP1 signaling pathway.

Exploring the Hypocholesterolemic Potential of a Fucus vesiculosus Extract: Omic Insights into Molecular Mechanisms at the Intestinal Level.

High blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells' metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids' metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract's compounds on intestinal cells.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. AIM OF THE STUDY: This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. MATERIALS AND METHODS: The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE-/- mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE-/- mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. CONCLUSION: This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

Meat quality of pigs fed grape pomace in different production systems.

The main objective of this study was to evaluate the effects of supplementation the diet of pigs with grape pomace preserved in silage form (GPS) and its interaction with indoor and outdoor production systems, with and without access to vegetation, on the attributes of meat quality produced. Analyzes of proximal composition, cholesterol content, fatty acid profile, shear force, texture profile and sensory analysis were performed. During cold storage, oxidative stability and objective color were analyzed. Statistical analysis was performed in a 3x2 factorial design (production systems (S) x GPS-feed (F)) and the interaction between them (S*F). The results showed that there was no interaction between the production system and GPS feeding for the attributes evaluated. The proximate composition and fatty acid profile of the muscle remained unchanged. Additionally, it provides higher subjective and objective tenderness, higher red color intensity, and reduces lipid oxidation under refrigeration. The supplementation of pig feed with GPS improve the quality of the meat and constitute a sustainable alternative for the winemaking residue.

Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet.

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.

Smilax China L. polysaccharide prevents HFD induced-NAFLD by regulating hepatic fat metabolism and gut microbiota.

BACKGROUND: The increasing incidence of nonalcoholic fatty liver disease (NAFLD) has urged the development of new therapeutics. NAFLD is intimately linked to gut microbiota due to the hepatic portal system, and utilizing natural polysaccharides as prebiotics has become a prospective strategy for preventing NAFLD. Smilax china L. polysaccharide (SCP) possesses excellent hepatoprotective and anti-inflammatory activity. However, its protective effects on NAFLD remains unclear. PURPOSE: The goal of this study was to explore the protective effects of SCP on high-fat diet (HFD)-induced NAFLD mice by regulating hepatic fat metabolism and gut microbiota. METHODS: Extraction and isolation from Smilax china L. rhizome to obtain SCP. C57BL/6 J mice were distributed to six groups: Control (normal chow diet), HFD-fed mice were assigned to HFD, simvastatin (SVT), and low-, medium-, high-doses of SCP for 12 weeks. The body, liver, and different adipose tissues weights were detected, and lipids in serum and liver were assessed. RT-PCR and Western blot were used to detect the hepatic fat metabolism-related genes and proteins. Gut microbiota of cecum contents was profiled through 16S rRNA gene sequencing. RESULTS: SCP effectively reversed HFD-induced increase weights of body, liver, and different adipose tissues. Lipid levels of serum and liver were also significantly reduced after SCP intervention. According to the results of RT-PCR and western blot analysis, SCP treatment up-regulated the genes and proteins related to lipolysis were up-regulated, while lipogenesis-related genes and proteins were down-regulated. Furthermore, the HFD-induced dysbiosis of intestinal microbiota was similarly repaired by SCP intervention, including enriching beneficial bacteria and depleting harmful bacteria. CONCLUSION: SCP could effectively prevent HFD-induced NAFLD, might be considered as a prebiotic agent due to its excellent effects on altering hepatic fat metabolism and maintaining gut microbiota homeostasis.

Gehua Jiejiu Dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study.

OBJECTIVE: To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction (, GJDD) on alcoholic fatty live disease (AFLD) by using proteomic methods. METHODS: The male C57BL/6J mouse were randomly divided into four groups: control group, model group, GJDD group and resveratrol group. After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method, the GJDD group and resveratrol group were intragastrically administered with GJDD (4900 mg/kg) and resveratrol (400 mg/kg) respectively, once a day for 9 d. The fat deposition of liver tissue was observed and evaluated by oil red O (ORO) staining. 4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group. The differentially expressed proteins were screened according to protein expression differential multiples, and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Finally, expression validation of the differentially co-expressed proteins from control group, model group and GJDD group were verified by targeted proteomics quantification techniques. RESULTS: In semiquantitative analyses of ORO, all kinds of steatosis (ToS, MaS, and MiS) were evaluated higher in AFLD mice compared to those in GJDD or resveratrol-treated mice. 4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified, of which 3763 proteins were quantified and 946 differentially expressed proteins were screened. Compared with the control group, 145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group. In addition, compared with the model group, 92 proteins were up-regulated and 135 proteins were down-regulated in the liver tissue of the GJDD group. 15 differentially co-expressed proteins were found between every two groups (model group vs control group, GJDD group vs model group and GJDD group vs control group), which were involved in many biological processes. Among them, 11 differentially co-expressed key proteins (Aox3, H1-5, Fabp5, Ces3a, Nudt7, Serpinb1a, Fkbp11, Rpl22l1, Keg1, Acss2 and Slco1a1) were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis. CONCLUSIONS: Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression, likely through the modulation of lipid metabolism, bile acid metabolism and with exertion of antioxidant stress.

Mechanisms of Dangua Fang in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.

OBJECTIVE: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. METHODS: Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. RESULTS: DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. CONCLUSION: DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.

Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. AIM OF THE STUDY: This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. METHODS: A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. RESULTS: Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. CONCLUSION: This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.

Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.

This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.

[Influence of the rat diet enrichment with oat ß-gucans on the assimilation of B group vitamins, mineral elements and lipid metabolism].

Despite the widespread use of oat ß-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of ß-glucans (ß-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of ß-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with ß-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of ß-glucans in the diet. At the same time, against the background of the presence of ß-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with ß-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of ß-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. AIM OF THE STUDY: Clarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. MATERIALS AND METHODS: A free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. RESULTS: The results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. CONCLUSION: For the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.

Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL/6J Mice.

Human milk is naturally rich in medium- and long-chain triacylglycerols (MLCT), accounting for approximately 30% of the total fat. However, infant formula fat is prepared using a physical blend of vegetable oils, which rarely contains MLCT, similar to human milk. The differences in MLCT between human milk and infant formulas may cause different lipid metabolisms and physiological effects on infants, which are unknown. This study aimed to analyze the metabolic characteristics of formula lipid containing novel human milk fat substitutes based on MLCT (FL-MLCT) and compare their effects with those of the physical blend of vegetable oils (FL-PB) on lipid metabolism and gut microbiota in mice. Compared with the FL-PB group, the FL-MLCT group showed increased energy expenditure, decreased serum triacylglycerol level, and significantly lower aspartate aminotransferase level, epididymal and perirenal fat weight, and adipocyte size. Moreover, the abundances of Firmicutes/Bacteroidota, Actinobacteriota, and Desulfovibrionaceae were significantly decreased in the FL-MLCT group. Novel human milk fat substitutes MLCT could inhibit visceral fat accumulation, improve liver function, and modulate the mice gut microbiota composition, which may contribute to controlling obesity.

GBA3 promotes fatty acid oxidation and alleviates non-alcoholic fatty liver by increasing CPT2 transcription.

BACKGROUND: Excessive lipids accumulation and hepatocytes death are prominent characteristics of non-alcoholic fatty liver disease (NAFLD). Nonetheless, the precise pathophysiological mechanisms are not fully elucidated. METHODS: HepG2 cells stimulated with palmitic acids and rats fed with high-fat diet were used as models for NAFLD. The impact of Glucosylceramidase Beta 3 (GBA3) on fatty acid oxidation (FAO) was assessed using Seahorse metabolic analyzer. Lipid content was measured both in vitro and in vivo. To evaluate NAFLD progression, histological analysis was performed along with measurements of inflammatory factors and liver enzyme levels. Western blot and immunohistochemistry were employed to examine the activity levels of necroptosis. Flow cytometry and reactive oxygen species (ROS) staining were utilized to assess levels of oxidative stress. RESULTS: GBA3 promoted FAO and enhanced the mitochondrial membrane potential without affecting glycolysis. These reduced the lipid accumulation. Rats supplemented with GBA3 exhibited lower levels of inflammatory factors and liver enzymes, resulting in a slower progression of NAFLD. GBA3 overexpression reduced ROS and the ratio of cell apoptosis. Phosphorylation level was reduced in the essential mediator, MLKL, implicated in necroptosis. Mechanistically, as a transcriptional coactivator, GBA3 promoted the expression of Carnitine Palmitoyltransferase 2 (CPT2), which resulted in enhanced FAO. CONCLUSIONS: Increased FAO resulting from GBA3 reduced oxidative stress and the production of ROS, thereby inhibiting necroptosis and delaying the progression of NAFLD. Our research offers novel insights into the potential therapeutic applications of GBA3 and FAO in the management and treatment of NAFLD.