High-fat Diet-induced Metabolic Disorders Research Articles

Chlorantraniliprole exposure aggravates high-fat diet-induced metabolic disorders in mice by regulating gut microbiota and its metabolites

Chlorantraniliprole exposure aggravates high-fat diet-induced metabolic disorders in mice by regulating gut microbiota and its metabolites

Protective effect of heat-processed Gynostemma pentaphyllum on high fat diet-induced glucose metabolic disorders mice.

Glucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney. Gynostemma pentaphyllum is commonly used in the clinical treatment of diabetes, but the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed Gynostemma pentaphyllum (HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.

High-Intensity Interval Training Ameliorates High-Fat Diet-Induced Metabolic Disorders via the Cyclic GMP-AMP Synthase-Stimulator of Interferon Gene Signaling Pathway.

Metabolic diseases are growing in prevalence worldwide. Although the pathogenesis of metabolic diseases remains ambiguous, the correlation between cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) and metabolic diseases has been identified recently. Exercise is an effective intervention protecting against metabolic diseases, however, the role of the cGAS-STING signaling pathway in this process is unclear, and the effect and mechanism of different exercise intensities on metabolic disorders are still unknown. Thus, we explored the association between exercise to ameliorate HFD-induced metabolic disorders and the cGAS-STING signaling pathway and compared the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Male C57BL/6 mice (6-8 weeks old) were fed HFD for 8 weeks to establish a metabolic disease model and were subjected to 8-week MICT or HIIT training. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were used to assess glucose metabolism. Serum triglyceride (TG) and total cholesterol (TC) were measured to evaluate lipid metabolism. Oil red staining was used to observe the lipid droplets in the gastrocnemius muscle. An enzyme-linked immunosorbent assay was used to detect the serum inflammatory factors IL-6 and IFN-β. The protein expression of the cGAS-STING signaling pathway was detected by the WesTM automatic protein expression analysis system. We reported that HFD induced metabolic disorders with obesity, abnormal glucolipid metabolism, and significant inflammatory responses. Both HIIT and MICT ameliorated the above adverse reactions, but MICT was superior to HIIT in improving glucolipid disorders. Additionally, HIIT significantly increased the expression of STING protein, as well as the phosphorylation of TBKI and the ratio of p-IRF3/IRF3. MICT only increased the expression of STING protein. Our findings suggest that HIIT may alleviate HFD-induced metabolic disorder phenotype through the cGAS-STING signaling pathway. However, the improvement of MICT on metabolic disorder phenotype is less associated with the cGAS-STING pathway, which needs to be further explored.

High Gamma-Aminobutyric Acid (GABA) Oolong Tea Alleviates High-Fat Diet-Induced Metabolic Disorders in Mice.

Obesity and overweight are associated with an increasing risk of developing health conditions and chronic non-communicable diseases, including cardiovascular diseases, cancer, musculoskeletal problems, respiratory problems, and mental health, and its prevalence is rising. Diet is one of three primary lifestyle interventions. Many bioactive components in tea especially oolong tea, including flavonoids, gamma-aminobutyric acid (GABA), and caffeine were reported to show related effects in reducing the risk of obesity. However, the effects of GABA oolong tea extracts (OTEs) on high-fat diet (HFD)-induced obesity are still unclear. Therefore, this study aims to explore whether the intervention of GABA OTEs can prevent HFD-induced obesity and decipher its underlying mechanisms using male C57BL/6 J mice. The result indicated that GABA OTEs reduced leptin expression in epididymal adipose tissue and showed a protective effect on nonalcoholic fatty liver disease. It promoted thermogenesis-related protein of uncoupling protein-1 and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), boosted lipid metabolism, and promoted fatty acid oxidation. It also reduced lipogenesis-related protein levels of sterol regulatory element binding protein, acetyl-CoA carboxylase, and fatty acid synthase and inhibited hepatic triglyceride (TG) levels. These data suggest that regular drinking of GABA oolong tea has the potential to reduce the risk of being overweight, preventing obesity development through thermogenesis, lipogenesis, and lipolysis.

Membrane estrogen receptor-α contributes to female protection against high-fat diet-induced metabolic disorders.

Estrogen Receptor α (ERα) is a significant modulator of energy balance and lipid/glucose metabolisms. Beyond the classical nuclear actions of the receptor, rapid activation of intracellular signaling pathways is mediated by a sub-fraction of ERα localized to the plasma membrane, known as Membrane Initiated Steroid Signaling (MISS). However, whether membrane ERα is involved in the protective metabolic actions of endogenous estrogens in conditions of nutritional challenge, and thus contributes to sex differences in the susceptibility to metabolic diseases, remains to be clarified. Male and female C451A-ERα mice, harboring a point mutation which results in the abolition of membrane localization and MISS-related effects of the receptor, and their wild-type littermates (WT-ERα) were maintained on a normal chow diet (NCD) or fed a high-fat diet (HFD). Body weight gain, body composition and glucose tolerance were monitored. Insulin sensitivity and energy balance regulation were further investigated in HFD-fed female mice. C451A-ERα genotype had no influence on body weight gain, adipose tissue accumulation and glucose tolerance in NCD-fed mice of both sexes followed up to 7 months of age, nor male mice fed a HFD for 12 weeks. In contrast, compared to WT-ERα littermates, HFD-fed C451A-ERα female mice exhibited: 1) accelerated fat mass accumulation, liver steatosis and impaired glucose tolerance; 2) whole-body insulin resistance, assessed by hyperinsulinemic-euglycemic clamps, and altered insulin-induced signaling in skeletal muscle and liver; 3) significant decrease in energy expenditure associated with histological and functional abnormalities of brown adipose tissue and a defect in thermogenesis regulation in response to cold exposure. Besides the well-characterized role of ERα nuclear actions, membrane-initiated ERα extra-nuclear signaling contributes to female, but not to male, protection against HFD-induced obesity and associated metabolic disorders in mouse.

Amuc attenuates high-fat diet-induced metabolic disorders linked to the regulation of fatty acid metabolism, bile acid metabolism, and the gut microbiota in mice

Amuc_1100 (hereafter called Amuc) is a highly abundant pili-like protein on the outer membrane of Akkermansia muciniphila and has been found to be effective for in anti-obesity, which is probably through the activation of TLR2. However, the precise mechanisms underlying the contributions of TLR2 to obesity resistance remain unknown. Here, TLR2 knockout mice were used to decipher the anti-obesity mechanism of Amuc. Mice exposed to a high-fat diet (HFD) were treated with Amuc (60 μg) every other day for 8 weeks. The results showed that Amuc supplementation decreased mouse body weight and lipid deposition by regulating fatty acid metabolism and reducing bile acid synthesis by activating TGR5 and FXR and strengthening the intestinal barrier function. The ablation of TLR2 partially reversed the positive effect of Amuc on obesity. Furthermore, we revealed that Amuc altered the gut microbiota composition by increasing the relative abundance of Peptostreptococcaceae, Faecalibaculum, Butyricicoccus, and Mucispirillum_schaedleri_ASF457, and decreasing Desulfovibrionaceae, which may serve as a contributor for Amuc to reinforce the intestinal barrier in HFD-induced mice. Therefore, the anti-obesity effect of Amuc was accompanied by the mitigation of gut microbes. These findings provide support for the use of Amuc as a therapy targeting obesity-associated metabolic syndrome.

Resveratrol-loaded selenium/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer's disease

Resveratrol (Res) is a common natural polyphenol that inhibits inflammation and oxidative stress in Alzheimer's disease (AD). However, the absorption efficiency and in vivo bioactivity of Res are poor. High fat diet-induced metabolic disorders, including obesity and insulin resistance, can promote AD-related β-amyloid (Aβ) aggregation, Tau protein phosphorylation and neurotoxicity. Gut microbiota play a role in modulating metabolic syndrome and cognitive impairment. Herein, flower-like Res-loaded selenium nanoparticles/chitosan nanoparticles (Res@SeNPs@Res-CS-NPs) with higher loading capacity (64 %) were prepared to regulate gut microbiota in cases of AD with metabolic disorder. The nano-flowers could restore gut microbiota homeostasis to reduce lipopolysaccharide (LPS) formation and LPS-induced neuroinflammation. Additionally, Res@SeNPs@Res-CS-NPs can prevent lipid deposition and insulin resistance by decreasing Firmicutes levels and increasing Bacteroidetes levels in the gut, further inhibiting Aβ aggregation and Tau protein phosphorylation through the JNK/AKT/GSK3β signaling pathway. Moreover, Res@SeNPs@Res-CS-NPs treatment was able to regulate the relative levels of gut microbiota associated with oxidative stress, inflammation and lipid deposition, including Entercoccus, Colidextribacter, Rikenella, Ruminococcus, Candidatus_Saccharimonas, Alloprevotella and Lachnospiraceae_UCG-006. Overall, Res@SeNPs@Res-CS-NPs significantly enhances cognitive ability in AD mice with metabolic disorder, highlighting their potential for preventing cognitive impairments in AD.

Inulin increases the beneficial effects of rhubarb supplementation on high-fat high-sugar diet-induced metabolic disorders in mice: impact on energy expenditure, brown adipose tissue activity, and microbiota

ABSTRACT Consumption of prebiotics and plant-based compounds have many beneficial health effects through modulation of gut microbiota composition and are considered as promising nutritional strategy for the treatment of metabolic diseases. In the present study, we assessed the separated and combined effects of inulin and rhubarb on diet-induced metabolic disease in mice. We showed that supplementation with both inulin and rhubarb abolished the total body and fat mass gain upon high-fat and high-sucrose diet (HFHS) as well as several obesity-associated metabolic disorders. These effects were associated with increased energy expenditure, lower whitening of the brown adipose tissue, higher mitochondria activity and increased expression of lipolytic markers in white adipose tissue. Despite modifications of intestinal gut microbiota and bile acid compositions by inulin or rhubarb alone, combination of both inulin and rhubarb had minor additional impact on these parameters. However, the combination of inulin and rhubarb increased the expression of several antimicrobial peptides and higher goblet cell numbers, thereby suggesting a reinforcement of the gut barrier. Together, these results suggest that the combination of inulin and rhubarb in mice potentiates beneficial effects of separated rhubarb and inulin on HFHS-related metabolic disease and could be considered as nutritional strategy for the prevention and treatment of obesity and related pathologies.

Alternate-Day High Fat-Normal Chow Diet Ameliorates HFD-Induced Obesity and Restores Intestinal Immunity.

To investigate the effect of alternating-day diet regimens on high-fat diet-induced metabolic disorders in mice. Eight-week-old C57BL/6J mice were fed with either a continuous normal chow diet (CD, n = 10), a continuous high-fat diet (HFD, n = 10), HFD alternating every 24 h with fasting (H-ADF, n = 20), or HFD alternating every 24 h with chow diet (H-ADC, n = 20) for 12 weeks. Weights were recorded weekly and oral glucose tolerance tests were performed 6 weeks after initiating the regimens. At the end of the study, blood samples were collected and serum insulin and lipids were measured; tissues were collected for histology and RNA-seq analysis. HFD significantly increased body weight and fat percentage, while HFD alternating with fasting or CD did not significantly affect body weight and fat percentage. The glucose intolerance induced by HFD was also significantly ameliorated in these two diet intervention groups. HFD-induced elevation of total cholesterol, low-density lipoprotein and insulin were also reduced in H-ADF and H-ADC groups. Moreover, HFD-disturbed immunity, presented by Lysozyme C-1 (Lyz1) immunostaining and RNA-seq, was restored in both alternating-regimen groups, especially, with H-ADC. At the transcriptional level, some cell proliferation and lipid absorption pathways were down-regulated in both H-ADF and H-ADC groups compared to the continuous HFD group. Alternating an HFD with a normal diet every 24 h effectively controls weight and prevents metabolic disorders and may act by affecting both fat absorption and intestinal immunity.

Baccharis trimera Infusion Reduces Macrophages Activation and High-Fat Diet-Induced Metabolic Disorders in Mice.

The aim of this study is to evaluate the efficacy of Baccharis trimera infusion on high-fat diet-induced metabolic disorders in mice and macrophages activation. This study evaluated obesity, insulin resistance, dyslipidemia and hepatic steatosis induced by a high-fat diet in Swiss mice. Cellular parameters in macrophages, such as cell viability (MTT), the production and release of nitric oxide (NO) and hydrogen peroxide (H2O2), cell spreading, cell adhesion and phagocytosis were determined. Our results showed that treatment with B. trimera prevented the mentioned conditions, except for the production of hydrogen peroxide. B. trimera prevented the development of obesity and associated comorbidities, as well as activation of macrophages. In conclusion, B. trimera is able to prevent obesity and metabolic disorders and macrophages activation, minimizing inflammation and validating the popular use of this plant tea.

Kynurenic acid ameliorates NLRP3 inflammasome activation by blocking calcium mobilization via GPR35.

The inflammasome has been linked to diverse inflammatory and metabolic diseases, and tight control of inflammasome activation is necessary to avoid excessive inflammation. Kynurenic acid (KA) is a tryptophan metabolite in the kynurenine pathway. However, the roles and mechanisms of the regulation of inflammasome activation by KA have not yet been fully elucidated. Here, we found that KA suppressed caspase-1 activation and IL-1β production in macrophages by specifically inhibiting canonical and noncanonical activation of the NLRP3 inflammasome. Mechanistically, KA reduced calcium mobilization through G-protein receptor 35 (GPR35), resulting in reduced mitochondrial damage and decreased mtROS production, thus blocking NLRP3 inflammasome assembly and activation. Importantly, KA prevented lipopolysaccharide-induced systemic inflammation, monosodium urate-induced peritoneal inflammation, and high-fat diet-induced metabolic disorder. Thus, KA ameliorated inflammation and metabolic disorders by blocking calcium mobilization-mediated NLRP3 inflammasome activation via GPR35. Our data reveal a novel mechanism for KA in the modulation of inflammasome activation and suggest that GPR35 might be a promising target for improving NLRP3 inflammasome-associated diseases by regulating calcium mobilization.

Preventive Effects of l-Glutamine on High-Fat Diet-Induced Metabolic Disorders Linking with Regulation of Intestinal Barrier Integrity, Hepatic Lipid Metabolism, and Gut Microbiota in Rats.

The present study was conducted to investigate the effects of l-glutamine (Gln) on a high-fat diet (HFD)-induced lipid metabolic abnormality and explore its possible mechanisms. The results demonstrated that Gln administration reduced body weight, improved serum lipids, and decreased glucose tolerance in HFD-fed rats. Meanwhile, Gln administration alleviated liver injury, reduced the hepatic inflammatory response by inhibiting NLRP3 inflammasome activation, and decreased hepatic lipid accumulation by promoting VLDL secretion and fatty acid β-oxidation, as well as reduced bile acid synthesis by activating hepatic and ileal FXR in HFD-fed rats. Moreover, Gln administration restored HFD-induced intestinal barrier dysfunction, promoted intestinal fat absorption, suppressed intestinal inflammation, and also reshaped the gut microbiota composition in HFD-fed rats by downregulating the abundance of potential pathogens Escherichia-Shigella and upregulating the abundance of beneficial bacteria such as Akkermansia. To conclude, the present results showed that Gln may be a potential option for preventing HFD-induced metabolic disorders via the gut-liver axis.

Exercise improves high-fat diet-induced metabolic disorder by promoting HDAC5 degradation through the ubiquitin–proteasome system in skeletal muscle

Histone deacetylase 4/5 (HDAC4/5) are essential for regulating metabolic gene expression; AMPKα2 regulates HDAC4/5 activity and the expression of MuRF1 during exercise. In this study, we used wild-type and AMPKα2-/- mice to explore the potential regulatory relationship between AMPKα2 and HDAC4/5 expression during exercise. Firstly, we fed C57BL/6J mice with high-fat diet for 8 weeks to assess the effects of high-fat diet on skeletal muscle metabolism and HDAC4/5 expression. We then performed a 6-week treadmill exercise on both wild-type and AMPKα2-/- mice. After exercise, the expressions of HDAC4/5 were examined in both gastrocnemius and soleus. The citrate synthase activity and proteins involved in skeletal muscle oxidative process were assessed. To determine the relationship of HDAC4/5 and skeletal muscle oxidative capacity, citrate synthase activity was assessed after silencing HDAC4/5. Moreover, HDAC5 ubiquitination and the association of MuRF1 to HDAC5 were also investigated. Our results showed that 6-week exercise increased the skeletal muscle oxidative capacity and decreased HDAC4/5 expression only in soleus. HDAC5 silencing increased C2C12 cell oxidative capacity. Proteasome inhibition by MG132 abolished exercise-induced HDAC5 degradation mediated by MuRF1-ubiquitin-proteasome system. However, the ubiquitin-proteasome system (UPS) did not dominantly account for exercise-induced HDAC4 degradation. Exercise upregulated MuRF1-HDAC5 association in wild-type mice but not in AMPKα2-/- mice. Our results revealed that 6-week exercise increased the skeletal muscle oxidative capacity and promoted HDAC5 degradation in soleus through the UPS, MuRF1-mediated HDAC5 ubiquitination. Although AMPKα2 played a partial role in regulating MuRF1 expression and HDAC5 ubiquitination, exercise-induced HDAC5 degradation did not fully depend on AMPKα2.

Differential modulations of lauric acid and its glycerides on high fat diet-induced metabolic disorders and gut microbiota dysbiosis

The anti-bacterial properties of lauric acid (LA) and its glycerides had been studied. However, their effects on gut microbiota remain unclear. Moreover, LA and its glycerides performed controversial influences on lipid metabolism. This study evaluated the regulation of LA, glycerol monolaurate (GML) and lauric triglyceride (GTL) on metabolic health and gut microbiota in high fat diet-fed mice. Serum metabolomics and lipidomics contributed to elucidate the underlying mechanisms. LA and its glycerides ameliorated hyperlipidemia, while GML performed more pronounced modulation on glucose metabolism and inflammation. LA and its glycerides modulated gut microbiota with increased Bifidobacterium and decreased Desulfovibrio, which closely related with metabolic improvements. Furthermore, the integrative multi-omics analyses identified that the regulation of phospholipid metabolism, intestinal microbial metabolites (bile acids and indole derivatives) and endogenous unsaturated fatty acids synthesis conduced to the more evident modulation of GML. Our findings suggested an effective strategy of GML for improving metabolism and gut health.

Indolepropionic acid reduces obesity-induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell-derived IL-25.

Previous studies have indicated that indolepropionic acid (IPA), derived from dietary tryptophan via gut microbiota conversion, is negatively correlated with type 2 diabetes mellitus and systemic low-grade inflammation. However, the effects of IPA administration on obesity, as well as the underlying mechanisms, remain unclear. In the present study, we observed that obesity leads to a dramatic reduction in IPA levels in both the serum and colonic mucosa, and IPA supplementation exerted beneficial effects on weight, as well as on glucose and lipid metabolism disorders. In adipose tissue, IPA treatment had no direct effect on adipocyte differentiation, but it significantly ameliorated adipose inflammation, thus preventing adipocyte enlargement. Moreover, IPA administration promoted gut integrity, increased the expression of tight junction proteins, and downregulated colonic inflammation; these effects were demonstrated to have a poor relationship with gut microbiota composition. Mechanistically, IPA significantly promoted the expansion of the tuft cell lineage in the gut and increased the secretion of interleukin-25 both in vivo and ex vivo, which contributes to the integrity of the gut barrier. This may partly depend on the free fatty acid receptor 3 pathway in tuft cells. Overall, our results demonstrate that IPA supplementation prevents the development of high-fat diet-induced obesity and metabolic disorders by restoring tuft cell-interleukin-25-mediated colonic barrier integrity; hence, IPA could be a potential agent for treatment of obesity.

Metabolomic and Microbial Remodeling by Shanmei Capsule Improves Hyperlipidemia in High Fat Food-Induced Mice.

Hyperlipidemia refers to a chronic disease caused by systemic metabolic disorder, and its pathophysiology is very complex. Shanmei capsule (SM) is a famous preparation with a long tradition of use for anti-hyperlipidemia treatment in China. However, the regulation mechanism of SM on hyperlipidemia has not been elucidated so far. In this study, a combination of UPLC-Q-TOF/MS techniques and 16S rDNA gene sequencing was performed to investigate the effects of SM treatment on plasma metabolism-mediated change and intestinal homeostasis. The results indicated that SM potently ameliorated high-fat diet-induced glucose and lipid metabolic disorders and reduced the histopathological injury. Pathway analysis indicated that alterations of differential metabolites were mainly involved in glycerophospholipid metabolism, linolenic acid metabolism, α-linoleic acid metabolism, and arachidonic acid metabolism. These changes were accompanied by a significant perturbation of intestinal microbiota characterized by marked increased microbial richness and changed microbiota composition. There were many genera illustrating strong correlations with hyperlipidemia-related markers (e.g., weight gains, GLU, and total cholesterol), including the Lachnospiraceae NK4A136 group and the Lachnospiraceae NK4B4 group. Overall, this study initially confirmed that hyperlipidemia is associated with metabolic disturbance and intestinal microbiota disorders, and SM can be employed to help decrease hyperlipidemia risk, including improving the abnormal metabolic profile and maintaining the gut microbial environment.

Maternal Dietary Betaine Prevents High-Fat Diet-Induced Metabolic Disorders and Gut Microbiota Alterations in Mouse Dams and Offspring From Young to Adult.

Early life is a critical window for preventing the intergenerational transmission of metabolic diseases. Betaine has been proven to play a role in improving glucose and lipid metabolism disorders in animal models. However, whether maternal betaine supplementation plays a role in regulating gut microbiota in both dams and offspring remains unclear. In this study, C57BL/6 female mice were fed with control diet (Ctr), high-fat diet (HF), and high-fat with betaine supplementation (0.3% betaine in the diet, HFB) from 3 weeks prior to mating and lasted throughout pregnancy and lactation. After weaning, the offspring got free access to normal chow diet until 20 weeks of age. We found that maternal dietary betaine supplementation significantly improved glucose and insulin resistance, as well as reduced free fatty acid (FFA) concentration in dams and offspring from young to adult. When compared to the HF group, Intestinimonas and Acetatifactor were reduced by betaine supplementation in dams; Desulfovibrio was reduced in 4-week-old offspring of the HFB group; and Lachnoclostridium was enriched in 20-week-old offspring of the HFB group. Moreover, the persistent elevated genus Romboutsia in both dams and offspring in the HFB group was reported for the first time. Overall, maternal betaine could dramatically alleviate the detrimental effects of maternal overnutrition on metabolism in both dams and offspring. The persistent alterations in gut microbiota might play critical roles in uncovering the intergenerational metabolic benefits of maternal betaine, which highlights evidence for combating generational metabolic diseases.

Effect of synbiotic supplementation on asprosin level in high fat diet-induced metabolic disorder in pregnant rats

Synbiotic supplementation can improve metabolic disorders. The aim of this study was to assess the impact of synbiotic supplementation on the levels of asprosin, lipid profile, glucose, and insulin resistance in pregnant rats fed a high-fat diet (HFD). Rats were divided into three groups: control group (fed base chow), HFD group, and HFD + synbiotic group. Levels of blood glucose, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and asprosin levels were measured. Birth weight of offspring in the HFD + synbiotic group was significantly lower than in the HFD group. Similarly, serum asprosin, insulin, insulin resistance, TG and total cholesterol levels in the HFD + symbiotic group were significantly lower than in the HFD group. Asprosin levels had a significant and positive correlation between food intake in the first ten days of the experiment and gestation period, fasting blood sugar (FBS), TG, and homeostatic model assessment (HOMA) index. Moreover, asprosin levels had a significant and negative correlation with HDL and insulin levels. Results showed, synbiotic supplementation has beneficial effects on obese animals and improves weight gain during pregnancy, pup birth weight, FBS, insulin resistance and lipid profile. These advantages of synbiotic supplementation could be mediated by reducing serum asprosin levels.

Effects of blended oils with different n-6/n-3 polyunsaturated fatty acid ratios on high-fat diet-induced metabolic disorders and hepatic steatosis in rats

This study investigated the effects of blended oils with different n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on the metabolic disorders and hepatic steatosis in high-fat diet-fed rats. The 1:1 group had significantly lower serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and lipoprotein lipase (LPL) levels than those of the Lard group. The 5:1 group had significantly lower serum LDL-C, LPL, and adiponectin (ADP) than those in the Lard group. Serum LDL-C, angiotensin II (Ang II), endothelin-1, LPL and ADP levels in the 1:1 and 5:1 groups were significantly lower than those in the normal control group. The 5:1 group had significantly lower serum ADP, Ang II, LPL and resistin levels than those in the 20:1 group. The 20:1 group had significantly higher serum TC, LDL-C, HDL-C, nitric oxide (NO), 3-nitrotyrosine, free fatty acid and LPL levels than those in the 1:1 ratio group. Blended oils with a low n-6/n-3 PUFA ratio improved metabolic disorders and hepatic steatosis by regulating lipid metabolism, adipokines, endothelial cell function, and liver lipid metabolism. Conversely, a high n-6/n-3 PUFA ratio had adverse effects on metabolic profiles in high-fat diet-fed rats.

Medium-chain triglycerides improve lipid metabolism in obese rats through increasing the browning of adipose tissue via sympathetic regulation.

This study aimed to determine the effect and mechanism of medium-chain triglycerides (MCTs) on promoting the browning of adipose tissue. A high-fat diet was fed to the Sprague-Dawley rats to induce obesity, then caprylic triglycerides (CYTs), capric triglycerides (CTs) and lauric triglycerides (LTs) were used to treat the obese rats for 12 weeks. The obesity phenotype and molecular changes related to browning were determined. The results showed that all three MCTs promoted the browning/beiging of the adipose tissues (brown and white adipose tissue), and lipolysis in these tissues was also increased, which ameliorated high-fat diet-induced lipid metabolic disorders in the obese rats. The LT group showed the highest expression levels of lipolysis- and browning/beiging-related proteins, followed by the CT group and CYT group. We speculate that the browning process may be related to sympathetic regulation and all the three MCT administration increased the secretion of neurotrophic factors both in the hypothalamus and adipose tissue. Then, intra-adipose sympathetic arborization increased, resulting in the activation of the sympathetic regulatory system in MCT groups, and the LT group also showed the highest sympathetic nerve fiber density, followed by the CT group and CYT group. We have for the first time found that the effect of medium-chain fatty acids on adipose tissue browning might be related to the types of fatty acids.