High-fat Mice Research Articles

Overweight Leads to an Increase in Vitamin E Absorption and Status in Mice.

This study investigates whether vitamin E (VE) deficiency in subjects with obesity could, at least partly, be due to a defect in VE intestinal absorption. Mice follow either a high-fat (HF) or a control (CTL) diet for 12 weeks. The study evaluates their VE status, the expression of genes encoding proteins involved in lipid and fat-soluble vitamin intestinal absorption, and VE absorption using a γ-tocopherol-rich emulsion. HF mice have a weight (+23.0%) and an adiposity index (AI, +157.0) superior to CTL mice (p<0.05). α-Tocopherol concentrations are higher in both plasma (+45.0%) and liver (+116.9%) of HF mice compared to CTL mice (p<0.05). α-Tocopherol concentration in the adipose tissue of HF mice is higher than that of CTL mice after correction by the AI (+72.4%, p<0.05). No difference is found in the expression of genes coding for proteins involved in intestinal lipid metabolism in fasting mice. After force-feeding, γ-tocopherol plasma concentration is higher in HF mice compared to CTL mice (+181.5% at 1.5h after force-feeding, p<0.05). HF mice display higher status and more efficient absorption of VE than CTL mice. VE absorption is thus likely not impaired in the early stages of obesity.

Dual PPAR-a/g enhances beta cell identity, preserving islet structure in HF-fed mice.

The pancreas suffers from lipotoxicity, which threatens the survival of pancreatic islets. Dual PPAR-alpha(a)/gamma(g) agonism is a promising method for treating type 2 diabetes. This study evaluated the effects of single PPAR-a and PPAR-g or their combined activation on pancreatic islet remodeling, beta-cell proliferation, identity, and maintenance in an experimental obesity model. Fifty three-month-old mice, randomly divided to receive the control (C) or high-fat (HF) diet for ten weeks, were then redivided for a four-week treatment: C, HF, HF-a (received the PPAR-a agonist), HF-g (PPAR-g agonist pioglitazone), and HF-d (PPAR-a/g agonists). The HF group was overweight, had oral glucose intolerance, showed a proinflammatory adipokine profile, exhibited increased alpha and beta cell masses, and islet gene expression compatible with compromised beta cell proliferation and favored dedifferentiation. All treatments reduced body weight, mitigated oral glucose intolerance, and produced an anti-inflammatory adipokine profile, which rescued islet cytoarchitecture, and beta cell function. Principal component analysis (PCA) revealed a shift in the antiapoptotic gene Bcl2 and beta cell proliferation genes (Pax4 and Neurog3) in HF-a. Conversely, HF-g and HF-d benefited from the upregulation of genes related to beta cell function (Fgf21, Glut2, and Glp1r), identity, and maintenance (Pdx1, Neurod1, Mafa, and Nkx6.1). The HF mice were glucose intolerant, showing islet hypertrophy and low beta cell identity-related genes. In contrast, PPAR activation rescued islet structure, and PCA showed that the PPAR-a/g combination was the most effective treatment because it favored beta cell function, identity, and maintenance-related genes, halting the T2DM spectrum in diet-induced obese mice.

Regulation of Cecal Microbiota and Improvement of Blood Lipids Using Walnut Non-Dairy Creamer in High-Fat Mice: Replacing Traditional Non-Dairy Creamer.

Non-dairy creamer is a class of microencapsulated powdered fats and oils that are widely used in the food industry. However, the oils used in it are hydrogenated vegetable oils, which contain large amounts of saturated fatty acids and are extremely harmful to the human body. This study investigated the effects of replacing hydrogenated vegetable oil with walnut oil to prepare walnut non-dairy creamer on lipid levels and intestinal microorganisms in mice. The results show that low-dose walnut non-dairy creamer significantly decreased the contents of TC and TG in serum and increased the content of HDL-C (p < 0.01). The contents of MDA, ALT, and AST were significantly decreased, while the content of SOD was increased (p < 0.01). The abundance of Firmicutes in the walnut non-dairy creamer group decreased, and the abundance of Bacteroidetes/Firmicutes (B/F) increased, which significantly increased the richness of Lactobacillus and Oscillospira (p < 0.01). Allobaculum richness was significantly decreased (p < 0.01). In conclusion, a low dose of walnut non-dairy creamer can effectively promote the metabolism of blood lipids in vivo, alleviate oxidative stress injury and lipid accumulation damage to mouse hepatocytes, and ameliorate the adverse effects of a high-fat diet on the intestinal microbiota of mice. This study provides a theoretical basis for the replacement of traditional non-dairy creamer and the research and development of walnut deep processing.

Widely Targeted Lipidomics and Microbiomics Perspectives Reveal the Mechanism of Auricularia auricula Polysaccharide's Effect of Regulating Glucolipid Metabolism in High-Fat-Diet Mice.

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders.

Combined analysis of gut microbiota and metabolomics in high-fat model mice fed with Chlorella pyrenoidosa peptides

Chlorella pyrenoidosa peptides (SISISVAGGGR, T1) can effectively alleviate obesity and related metabolic disorders in high-fat mice. However, their lipid-lowering mechanism is still unclear. This research endeavor sought to delve into the potential mediators of T1 anti-obesity in high-fat mice through macrogenomics analyses combined with untargeted metabolomics analyses. The results showed that T1 alleviated HFD-induced increases in body weight, epididymal fat weight, TG, LDL, AST, TNF-α, and IL-1β levels, and increased HDL level. Moreover, T1 reversed the HFD-induced gut microbiota dysbiosis. Specifically, T1 resulted in a massive proliferation of Bacteroides, Parabacteroides, and Alistipes, as well as increased levels of metabolites such as DL-arginine, N-stearoyl GABA, and decreased levels of 7α,24(S)-dihydroxy-4-cholesten-3-one, and hexadecanedioic acid. Correlation analysis showed that T1 alleviated HFD-induced obesity metabolic syndrome and associated inflammation by modulating specific gut microbiota and related metabolites. This provides new ideas for the treatment of diet-induced obesity and related metabolic disorders.

Lipid-lowering effect and oral transport characteristics study of curculigoside.

The incidence of metabolic disorders during pregnancy is increasing year by year, with diseases including hypertension and hyperlipidemia. Statins are the primary drugs for treating hyperlipidemia or atherosclerosis, yet some patients remain unresponsive to them, and pregnant women are prohibited from taking statins. Curculigoside is the major biologically active natural product present in Curculigo orchioides. In this study, A high-fat mice model was developed to study the lipid-lowering effect of curculigoside. Using intestinal Caco-2 cell monolayer, the curculigoside transport properties at two temperatures and possible transporters were systemically studied. Curculigoside at concentrations used during the experiments have no toxic effect to Caco-2 cells. The curculigoside transfer from the apical to the basolateral side was strongly influenced by temperature. P-glycoprotein, breast cancer resistance protein, and efflux transporters are crucial components of the human intestinal cell line Caco-2. The curculigoside can significantly affect the contents of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in mice. The transport properties and potential mechanism of curculigoside offer valuable insights for the design of development of hypolipidemic drugs like anti-atherosclerotic drugs and also be helpful to the further study of the pharmacological activity of curculigoside.

Multi-omics analysis reveals the mechanism of Lacticaseibacillus paracasei IMAUJBC1 in alleviating hyperlipidemia

This study investigated the alleviating effect of Lacticaseibacillus paracasei IMAUJBC1 on hyperlipidemia and explored the associated mechanism by combining microbiome, transcriptomic, and lipomic analyses. The high-fat mouse model was established with a high-fat diet (HFD), and the intervention of IMAUJBC1 was conducted for 8 weeks after modeling. The results showed that IMAUJBC1 inhibited weight gain and liver fat accumulation in HFD mice, reduced total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) serum levels, promoted the conversion of liver cholesterol to total bile acid (TBA), and increased fecal T-CHO excretion. The IMAUJBC1 intervention decreased the ratio of Firmicutes and Bacteroidetes, while the abundance of Alistipes was increased in the mice intestinal microbiome. IMAUJBC1 may alleviate hyperlipidemia through the PPAR signaling pathway, fat digestion and absorption, cholesterol metabolism, and glycerophospholipid metabolism. In summary, IMAUJBC1 can be used as a functional lactobacillus to intervene in hyperlipidemia.

Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice†.

Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring's gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF dietalone.

Echinacoside Exerts Antihepatic Fibrosis Effects in High-Fat Mice Model by Modulating the ACVR2A-Smad Pathway.

Nonalcoholic steatohepatitis (NASH) is an increasingly common chronic liver disease in which hepatic fibrosis is the major pathological change. The transforming growth factor β (TGF-β)/mall mothers against decapentaplegic (Smad) signaling is the main effector of fibrosis. Although the antifibrotic effect of echinacoside (Ech) on the liver has been indicated previously, the cellular and molecular mechanisms remain unclear. This study aims to investigate both in vivo and in vitro antifibrotic properties of Ech. Cell viability and scratch/wound assays show that Ech significantly inhibits the proliferation, migration, and activation of human hepatic stellate LX-2 cells. In mice with high-fat diet-induced hepatic fibrosis, Ech treatment attenuates the progression of liver injury, inflammation, and fibrosis. Furthermore, transcriptome analysis and subsequent functional validation demonstrate that Ech achieves antifibrotic effects by the activin receptor type-2A (ACVR2A)-mediated TGF-β1/Smad signaling pathway; ultimately, ACVR2A is demonstrated to be an important target for hepatic fibrosis by inhibiting and inducing the expression of ACVR2A in LX-2 cells. Ech exerts potent antifibrotic effects by inhibiting the ACVR2A-mediated TGF-β1/Smad signaling axis and may serve as an alternative treatment for hepatic fibrosis.

Effects of konjac glucomannan intake patterns on glucose and lipid metabolism of obese mice induced by a high fat diet.

Konjac glucomannan (KGM) is a dietary fiber supplement that exhibits multiple biological activities, including weight control as well as regulation of glucose and lipid metabolism. Currently, KGM intake patterns in practical applications include KGM sol, thermal irreversible gel, and frozen thermal irreversible gel. In this study, four intake patterns of KGM, namely KGM sol (KS), deacetylated KGM (DK), KGM gel (KG), and frozen KGM gel (FKG), were used as materials to explore the effects of different KGM intake patterns on glucose and lipid metabolism and intestinal flora in obese mice induced by a high fat diet under the same dose. The results showed that any type of KGM intake could reduce body weight, fat mass, lipid levels, and insulin resistance in obese mice, and alleviate liver damage and inflammation caused by obesity. However, KS has the most significant effect on controlling blood glucose and blood lipid in obese mice. Additionally, it was found that KS, DK, KG and FKG can increase the α-diversity of intestinal microflora in high-fat mice and improve the microflora disorder in high-fat mice. Finally, KS may increase the levels of fasting appetite hormones GLP-1 and PYY in mice, up-regulate the expression of LDLR, GCK and G-6-pase mRNA, and increase the production of short-chain fatty acids (SCFAs) in the intestinal flora of mice, thus regulating glucose and lipid metabolism. This study systematically investigated the effects of different intake forms of KGM on metabolism and intestinal flora in obese mice, which is of great significance for further understanding the role of KGM in the prevention and treatment of obesity-related metabolic diseases and for developing targeted dietary interventions.

Gut Microbiota Depletion Using Antibiotics to Investigate Diet-Derived Microbial Metabolites: An Efficient Strategy.

Gut microbiota depletion using antibiotics in drinking water is a valuable tool to investigate the role of gut microbes and microbial metabolites in health and disease. However, there are challenges associated with this model. Animals avoid drinking water because of the antibiotic bitterness, which affects their metabolic health. The present study develops an efficient strategy to deplete gut microbes without affecting metabolic parameters. Male C57BL/6J mice (7 weeks old) are fed a control (C) or high-fat (HF) diet. Subgroups of C and HF mice receive an antibiotic cocktail in drinking water (CA and HA). The antibiotic dosage is gradually increased so that the animals adapt to the taste of antibiotics. Metabolic parameters, gut microbiome, and microbial metabolites are assessed after 12 weeks treatment. Culture methods and 16s rRNA amplification confirm the depletion of gut microbes in antibiotic groups (CA and HA). Further, antibiotic treatment does not alter metabolic parameters (body weight, body fat, lean body mass, blood glucose, and glucose/insulin tolerance), whereas it suppresses the production of diet-derived microbial metabolites (trimethylamine and trimethylamine-N-oxide). This strategy effectively depletes gut microbes and suppresses the production of microbial metabolites in mice without affecting their metabolic health.

Effects of Diet Macronutrient Composition on Weight Loss during Caloric Restriction and Subsequent Weight Regain during Refeeding in Aging Mice.

Caloric restriction (CR) induces weight loss, but is associated with rapid weight regain upon return to ad libitum feeding. Our aim was to investigate effects of the macronutrient composition of the diet on weight loss and regain in elderly mice. Males, 18 months old, of the C57BL/6J strain were subjected to 4-week 30% CR followed by 4 weeks of ad libitum refeeding on either high-carb (HC), high-fat (HF) or high-protein (HP) diets (n = 22 each). Mice (n = 11) fed a chow diet ad libitum served as a control group (CON). Body mass and food intake were monitored daily. Twenty-four-hour indirect calorimetry was used to assess energy expenditure and substrate oxidation. Muscle and fat mass were evaluated with dissection of the tissues. Serum leptin and ghrelin levels were also measured. CR-induced weight loss did not differ between the diets. Weight regain was particularly fast for HF as mice overshot their initial weight by 12.8 ± 5.7% after 4-week refeeding when HC and HP mice reached the weight of the CON group. Weight regain strongly correlated with energy intake across the groups. The respiratory exchange ratio was lower in HF mice (0.81 ± 0.03) compared to HC (0.94 ± 0.06, p < 0.001), HP (0.89 ± 0.04, p < 0.001) and CON mice (0.91 ± 0.06, p < 0.01) during the refeeding. Serum leptin levels were higher in HF mice (1.03 ± 0.50 ng/mL) compared to HC (0.46 ± 0.14, p < 0.001), HP (0.63 ± 0.28, p < 0.05) or CON mice (0.41 ± 0.14, p < 0.001). Thus, CR induces similar weight loss in aging mice irrespective of the diet's macronutrient composition. An HF diet leads to excessive energy intake and pronounced gain in body fat in spite of increased fat oxidation and serum leptin during the refeeding after CR.

High-Fat Mouse Model to Explore the Relationship between Abnormal Lipid Metabolism and Enolase in Pancreatic Cancer.

Malignant tumors have become a major social health problem that seriously threatens human health, among which pancreatic cancer has a high degree of malignancy, difficult diagnosis and treatment, short survival time, and high mortality. More and more attention has been paid to abnormal lipid metabolism as a momentous carcinogenesis mechanism. Here, we explored the relationship between abnormal lipid metabolism, enolase, and pancreatic cancer by clinical data analysis. A high-fat mouse model was constructed, and then, a subcutaneous tumorigenesis mouse model of carcinoma of pancreatic cells and a metastatic neoplasm mouse pattern of pancreatic carcinoma cells injected through the tail vein were constructed to explore whether abnormal lipid metabolism affects the progression of pancreatic cancer in mice. We constructed a high-lipid model of pancreatic carcinoma cell lines and knockdown and overexpressed enolase in pancreatic carcinoma cell lines and investigated whether high lipid regulates epithelial-mesenchymal transition (EMT) by upregulating enolase (ENO), thereby promoting the cells of pancreatic carcinoma to invade and migrate. Triglycerides, total cholesterol, free cholesterin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and neuron-specific enolase (NSE) from pancreatic cancer patients and nonpancreatic cancer patients were tested. The differences in blood lipids between patients with and without pancreatic carcinoma were compared, and the correlation between blood lipids and neuron-specific enolase was analyzed. We confirmed that the serum triglyceride level of pancreatic cancer patients at initial diagnosis is overtopping nonpancreatic cancer patients, and the neuron-specific enolase level of patients with pancreatic carcinoma is better than nonpancreatic carcinoma sufferers. Triglyceride level is positively correlated with neuron-specific enolase level, and serum triglyceride level has predictive value for pancreatic cancer. Hyperlipidemia can promote tumor growth and increase the expression levels of ENO1, ENO2, and ENO3 in subcutaneous tumor formation of pancreatic cancer in mice. Additional hyperlipidemia promoted pancreatic carcinoma metastasis in the lung in mice injected through the tail vein, which confirmed that hyperlipidemia accelerated the process of EMT by increasing the expression of ENO1, ENO2, and ENO3, therefore promoting the pancreatic cancer cell metastasis.

Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway.

In addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation. For this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta. Returning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. Improving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway.

The transcriptome reveals the molecular regulatory network of primordial follicle depletion in obese mice

To explore the dynamic transcriptional regulatory network of primordial follicle fate in obese mice to elucidate the potential mechanism of primordial follicle depletion. Experimental study and transcriptomic analysis. Healthy (n=15) and obese (n=15) female mice. Six-week-old CD-1 mice were divided into healthy and high-fat diet groups and fed continuously for 12 weeks. The diet of healthy mice contained 10% fat. The diet of high-fat mice contained 60% fat. Primordial to primary follicle transition rate, gene expression changes, enriched Kyoto Encyclopedia of Genes and Genomes pathways, and ferroptosis. Primordial follicle depletion was increased in the ovaries of obese mice. We found that deposited fat around primordial and primary follicles of obese mice was higher than that for healthy mice. The proliferation of granulosa cells around primary follicles was increased in obese mice. In addition, we uncovered specific gene signatures associated with the primordial to primary follicle transition (PPT) in obese mice using laser capture microdissection RNA sequencing analysis. Gene set enrichment analysis indicated that ferroptosis, cell oxidation, vascular endothelial growth factor, and mammalian target of rapamycin signaling were increased significantly in the primordial follicles of obese mice. Notably, the ferritin, acyl CoA synthetase long-chain family member 4, and solid carrier family 7 member 11 associated proteins of the ferroptosis signaling pathway were significantly increased in the PPT phase of obese mice. Our work suggests that ferroptosis is a key pathway activated within immature ovarian follicles in the context of obesity and that the process may be involved in the physiological regulation of the PPT as well.

Artificial non-nutritive sweeteners consumption is able to modulate glycemic control and body composition in healthy or diet-induced obese mice

Non-nutritive sweeteners (NNS) are among the most widely used food additives worldwide. Their substitution to sugar is presented as one of the solutions to prevent cardiometabolic disease, especially as they have a sweet taste but very low-energy content. However, several recent studies have questioned their physiological inactivity, which was the basis for their approval by health authorities. The main objective of this study was to evaluate the acute and chronic effects of artificial NNS consumption on glycemic control in lean and diet-induced mice models. Consequently, we evaluated the acute effects of NNS acesulfame-potassium (aceK) and sucralose on glucose tolerance, insulin sensitivity and insulin secretion measured in blood and at the beta-cells pancreatic level of mice. In another set of mice, we compared the effects of aceK or sucralose supplementations to sugar consumption during a 12 week long high-fat (HF) diet. At the end of the 12 weeks of supplementation, we evaluated the influence of these different conditions on glucose metabolism and body fat distribution. First, we reported, in our mice models, that oral glucose tolerance tests (OGTTs) after acute sucralose gavage were improved significantly compared to AceK gavage and control situation (vehicle). These acute effects on blood glucose levels after sucralose ingestion were not directly explained by a significant increase neither in beta cells insulin secretion nor in insulin sensitivity. Interestingly, we further demonstrated that both NNS chronic consumption were able to attenuate significantly the deleterious effect of HF diet on glycemic control (glucose tolerance and insulin sensitivity), independently of caloric intake. Moreover, we reported in HF mice supplemented with NNS a lower accumulation of adipose tissue in the inguinal and subcutaneous compartments which was associated with a reduction in body mass in these groups. Surprisingly, our results demonstrate that even an acute consumption of widely used NNS sucralose and AceK is able to alter glucose metabolism. When repeated over time, the consumption of these NNS also seems to be able to reduce deleterious effects of HF diet on glycemic control but also on body composition. These results may contribute to a better understanding of the effects of NNS on metabolic health, but further studies are needed to decipher underlying mechanisms.

Bamboo shoot dietary fiber alleviates gut microbiota dysbiosis and modulates liver fatty acid metabolism in mice with high-fat diet-induced obesity.

Obesity is a common nutritional disorder characterized by an excessive fat accumulation. In view of the critical role of gut microbiota in the development of obesity and metabolic diseases, novel dietary therapies have been developed to manage obesity by targeting the gut microbiome. In this study, we investigated anti-obesity effects of bamboo shoot dietary fiber (BSDF) and the potential mechanisms. After 12 weeks of intervention with BSDF in high-fat mice, we detected obesity-related phenotypic indicators, and made transcriptomic analysis of liver tissue. Then we analyzed the changes of gut microbiota using 16S rRNA gene sequencing, explored the effect of BSDF on gut microbiota metabolites, and finally verified the importance of gut microbiota through antibiotic animal model. We found that BSDF was effective in reducing lipid accumulation in liver and adipose tissue and alleviating dyslipidemia and insulin resistance. Liver transcriptome analysis results showed that BSDF could improve lipid metabolism and liver injury by modulating peroxisome proliferator-activated receptor (PPAR) and fatty acid metabolic pathways. The 16S rRNA gene sequencing analysis of gut microbiota composition showed that BSDF significantly enriched beneficial bacteria such as Bifidobacterium, Akkermansia, Dubosiella, and Alloprevotella. Analysis of fecal metabolomics and gut microbiota metabolites revealed that BSDF increased the levels of several short-chain fatty acids and enriched bile acids, which may be important for improving lipid metabolism. Notably, the obesity-related metabolic disorders were abrogated after the abrogation of gut microbiota, suggesting that gut microbiota is a key factor in the beneficial effects of BSDF. Our study suggests that BSDF as a prebiotic supplement has the potential to improve obesity by improving gut microbiota and modulating host PPAR and fatty acid metabolic pathways.

PM2.5 induce myocardial injury in hyperlipidemic mice through ROS-pyroptosis signaling pathway

Exposure to particulate matters with diameters below 2.5 µm (PM2.5) is considered a major risk factor for cardiovascular diseases (CVDs). The closest associations between PM2.5 and CVDs have been observed in hyperbetalipoproteinemia cases, although the detailed underpinning mechanism remains undefined. In this work, hyperlipidemic mice and H9C2 cells were used to examine the effects of PM2.5 on myocardial injury and their underlying mechanisms. The results revealed that PM2.5 exposure caused severe myocardial damage in the high-fat mouse model. Oxidative stress and pyroptosis were also observed along with myocardial injury. After inhibiting pyroptosis with disulfiram (DSF), the level of pyroptosis was effectively reduced as well as myocardial injury, suggesting that PM2.5 induced the pyroptosis pathway and further caused myocardial injury and cell death. Afterwards, by suppressing PM2.5-induced oxidative stress with N-acetyl-L-cysteine (NAC), myocardial injury was markedly ameliorated, and the upregulation of pyroptosis markers was reversed, which indicated that PM2.5-pyroptosis was also improved. Taken together, this study revealed that PM2.5 induce myocardial injury through the ROS-pyroptosis signaling pathway in hyperlipidemia mice models, providing a potential approach for clinical interventions.

Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver.

Metabolic and molecular interactions between branched-chain amino acid (BCAA) and lipid metabolism are evident in insulin-resistant tissues. However, it remains unclear whether insulin resistance is a prerequisite for these relationships and whether BCAAs or their metabolic intermediates can modulate hepatic lipid oxidation and synthesis. We hypothesized that BCAAs can alter hepatic oxidative function and de novo lipogenesis, independent of them being anaplerotic substrates for the mitochondria. Mice (C57BL/6NJ) were reared on a low-fat (LF), LF diet plus 1.5X BCAAs (LB), high-fat (HF) or HF diet plus 1.5X BCAAs (HB) for 12 wk. Hepatic metabolism was profiled utilizing stable isotopes coupled to mass spectrometry and nuclear magnetic resonance, together with fed-to-fasted changes in gene and protein expression. A greater induction of lipid oxidation and ketogenesis on fasting was evident in the BCAA-supplemented, insulin-sensitive livers from LB mice, whereas their rates of hepatic de novo lipogenesis remained lower than their LF counterparts. Onset of insulin resistance in HF and HB mice livers blunted these responses. Whole body turnover of BCAAs and their ketoacids, their serum concentrations, and the ketogenic flux from BCAA catabolism, all remained similar between fasted LF and LB mice. This suggested that the impact of BCAAs on lipid metabolism can occur independent of them or their degradation products fueling anaplerosis through the liver mitochondria. Furthermore, the greater induction of lipid oxidation in the LB livers accompanied higher mitochondrial NADH/NAD+ ratio and higher fed-to-fasting phosphorylation of AMPKα and ACC. Taken together, our results provide evidence that BCAA supplementation, under conditions of insulin sensitivity, improved the feeding-to-fasting induction of hepatic lipid oxidation through changes in cellular redox, thus providing a favorable biochemical environment for flux through β-oxidation and lower de novo lipogenesis.NEW & NOTEWORTHY Branched-chain amino acids (BCAAs) have been shown to modulate lipid metabolic networks in various tissues, especially during insulin resistance. In this study we show that the dietary supplementation of BCAAs to normal, insulin-sensitive mice resulted in higher mitochondrial NADH:NAD+ ratios and AMPK activation in the liver. This change in the cellular redox status provided an optimal metabolic milieu to increase fatty acid oxidation while keeping the rates of de novo lipogenesis lower in the BCAA-supplemented mice livers.

Beneficial Effects of Fermentation of Red Chili Pepper Using Lactococcus lactis subs. Cremoris RPG-HL-0136 in High-Fat Diet-Induced Obese Mice

Red chili pepper is a beneficial natural spicy food that has antiobesity and antitype II diabetes effects, but it is not conducive to in-depth research as a dietary strategy to treat obesity. This study aims to investigate the beneficial effects of red chili pepper, fermented with a novel Lactococcus lactis subs. cremoris RPG-HL-0136. LC-MS/MS analysis is conducted to detect the content of capsaicin and dihydrocapsaicin, and no significant difference is observed between the nonfermented red chili pepper (NFP) (W/W) and the prepared L. lactis subs. cremoris RPG-HL-0136-fermented chili mixture (LFP). After establishing a high-fat diet-induced obese type II diabetic mouse model, the effects on weight gain, weight loss of liver and testicular fat, total cholesterol, triglyceride, fasting glucose, insulin, and homeostatic model assessment for insulin resistance in LFP were evaluated to be better than those in NFP following 10 weeks of interventions. All animal experiments were approved by the Institutional Animal Care and Use Committee of Xinxiang medical university. NFP and LFP could increase the expression of transient receptor potential vanilloid subfamily 1, peroxisome proliferator-activated receptor-alpha and caspase-2 in the high-fat mice. Compared with unfermented red chili pepper, the fermented red chili pepper complex significantly reduced LPS, tumor necrosis factor-alpha, and interleukin-6 in serum (P < .05). Intake of LFP significantly increased the expression of claudin-1 and occludin in the colon of the high-fat mice (P < .05), and there was no damage to the stomach and colon. This study provides scientific evidence that red chili pepper, fermented with L. lactis subs. cremoris RPG-HL-0136, may be beneficial for future treatment of obesity and accompanying diabetes. (IACUC.No.XYLL-20200019).