High-fat Diet-induced Obese Mice Research Articles

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1β in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat diet-induced obese mice

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat diet-induced obese mice

Quercetin ameliorates hepatic fat accumulation in high-fat diet-induced obese mice via PPARs.

As a natural pigment in food, quercetin possesses multiple biological activities and plays a crucial role in regulating metabolic syndrome. Herein, we aim to explore the potential mechanism of quercetin to ameliorate hepatic fat accumulation. In vivo experiments showed that quercetin significantly relieved inflammation response by decreasing the serum TNF-α and IL-6 levels and also improved high-fat diet-induced hepatic steatosis without other organ injuries. Quercetin can effectively reduce lipid aggregation and down-regulate the protein expression of PCK1 in HepG2 cells induced by oleic acid and palmitic acid, indicating that inhibiting gluconeogenesis leads to hepatic fat accumulation reduction. Furthermore, molecular docking results suggested that quercetin can bind to both PPARα and PPARγ, with an even more potent binding affinity than indeglitazar, a pan-agonist of PPARs. In conclusion, quercetin may regulate gluconeogenesis to ameliorate hepatic fat accumulation via targeting PPARα/γ.

Mentha canadensis attenuates adiposity and hepatic steatosis in high-fat diet-induced obese mice.

Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.

A comparison between partially peeled hulless barley and whole grain hulless barley: beneficial effects on the regulation of serum glucose and the gut microbiota in high-fat diet-induced obese mice.

Though the hypoglycemic effect of whole grain hulless barley (Hordeum vulgare L.) has been documented, whether glucose metabolism would be improved by hulless barley with moderate peeling is still unclear. The purpose of this study was to compare the differences in glucose metabolism and gut microbiota between partially (10%) peeled hulless barley (PHB) and whole grain hulless barley (WHB) intervention in obese mice induced by a high-fat diet. The results showed that both PHB and WHB interventions significantly improved the impaired glucose tolerance, fat accumulation in fat and liver tissues, and the impaired intestinal barrier in mice. The dysbiosis of gut microbiota was improved and the relative abundance of some beneficial bacteria such as genera Lactobacillus, Bifidobacterium, Ileibacterium, and norank_f__Mutibaculaceae was increased by both, PHB and WHB, interventions. Spearman correlation analysis revealed that the abundance of Bifidobacterium was negatively correlated with the area under the blood glucose curve. In conclusion, our results provide evidence that hulless barley improved the gut microbiota and impaired glucose tolerance in mice, and also showed that there was little loss of hypoglycemic effect even when hulless barley was moderately peeled.

Cardiovascular and lipid-lowering effects of a marine lipoprotein extract in a high-fat diet-induced obesity mouse model.

Obesity is a major health challenge worldwide, with implications for diabetes, hypertension and cardiovascular disease (CVD). Regular consumption of dark-meat fish is linked to a lower incidence of CVD and associated metabolic disorders due to the presence of long-chain omega-3 fatty acid ethyl esters in fish oils. The aim of the present study was to determine whether a marine compound like a sardine lipoprotein extract (RCI-1502), regulates fat accumulation in the heart of a high-fat diet-induced (HFD) mouse model of obesity. To investigate its effects in the heart and liver, we conducted a randomized, 12-week placebo-controlled study in which we analyzed the expression of vascular inflammation markers, obesity biochemical patterns and related CVD pathologies. Male HFD-fed mice treated with a RCI-1502-supplemented diet showed reduced body weight, abdominal fat tissue and pericardial fat pad mass density without systemic toxicity. RCI-1502 significantly reduced triacylglyceride, low-density lipoprotein and total-cholesterol concentrations in serum, but increased HDL-cholesterol levels. Our data show that RCI-1502 is beneficial for reducing obesity associated with a long-term HFD, possibly by exerting a protective effect on lipidic homeostasis, indicated also by histopathological analysis. These results collectively indicate that RCI-1502 acts as a cardiovascular therapeutic nutraceutical agent, which modulates fat-induced inflammation and improves metabolic health.

Anti-Obesity Effects and the Regulation of Energy Metabolism in Skeletal Muscle Tissues of Allii Fistulosi Bulbus Extract in High Fat Diet-Induced Obesity Mice

Anti-Obesity Effects and the Regulation of Energy Metabolism in Skeletal Muscle Tissues of <i>Allii Fistulosi Bulbus</i> Extract in High Fat Diet-Induced Obesity Mice

Effects of Different Intensities of Treadmill Exercise on Neuroinflammation and Neurotrophic Factors in High-Fat Diet-Induced Obese Mice

Obesity can impair brain health and regular exercise can effectively improve brain function. However, verification of the subclinical effects of exercise in different exercise intensities is limited. This study aimed to verify the effect of different intensities of treadmill exercise on hippocampal neuroinflammatory markers and neurotrophic factors in high-fat diet (HFD)-induced obese mice. Forty C57/black male mice received a 4-week standard diet (control, CON; n = 10) or high-fat diet (HFD; n = 30) to induce obesity. Thereafter, the HFD group was subdivided equally into the HFD + sedentary (HFDS), HFD + moderate-intensity exercise (HFDME), and HFD + high-intensity exercise (HFDHE) groups (n = 10 each). Treadmill exercises of different intensities were conducted for 8 weeks. After 8 weeks of intervention, hippocampal interferon-gamma (IFN)-γ levels were significantly lower in the CON group than in the HFDS and HFDME groups (p 0.05), and the HFDHE group showed significantly lower IFN-γ levels than the HFDS group (p 0.05). In addition, hippocampal nerve growth factor levels were significantly higher in the HFDME and HFDHE groups than in the CON and HFDS groups (p 0.05). Collectively, these results suggest that obesity can induce neuroinflammation, and regular exercise can alleviate neuroinflammation and induce an increase in the expression of neurotrophic factors regardless of exercise intensity.

Adipocytolytic Polymer Nanoparticles for Localized Fat Reduction.

The demand for body fat reduction is increasing. However, conventional lipolytic approaches fail to control adipose tissue reduction and cause severe side effects in adjacent nonadipose tissues. A strategy to specifically reduce subcutaneous fat using adipocytolytic polymer nanoparticles in a minimally invasive manner is reported here. The polymer nanoparticles are designed to generate carbon dioxide gas when selectively absorbed by adipocytes. The carbon dioxide gas generated within late endosomes/lysosomes induces adipocytolysis, thereby reducing the number of cells. Localized injection of the adipocytolytic nanoparticles substantially reduces subcutaneous fat in a high-fat diet-induced obese mouse model, without significant changes in hematological or serum biochemical parameters. The adipocytolytic efficacy of the nanoparticles is also evaluated in a porcine model. This strategy addresses the need to develop safe and effective adipocytolytic agents using functional polymer nanoparticles.

Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders

ObjectiveHigh intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders.ResultsOral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the monocarboxylate transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport.ConclusionsOur data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota.A36-Fe9THWYcJRZtLBDMvSVideo

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice.

Obesity is a chronic peripheral inflammation condition that is strongly correlated with neurodegenerative diseases and associated with exposure to environmental chemicals. The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor activated by environmental chemical, such as dioxins, and also is a regulator of inflammation through interacting with nuclear factor (NF)-κB. In this study, we evaluated the anti-obesity and anti-inflammatory activity of HBU651, a novel AhR antagonist. In BV2 microglia cells, HBU651 successfully inhibited lipopolysaccharide (LPS)-mediated nuclear localization of NF-κB and production of NF-κB-dependent proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also restored LPS-induced mitochondrial dysfunction. While mice being fed a high-fat diet (HFD) induced peripheral and central inflammation and obesity, HBU651 alleviated HFD-induced obesity, insulin resistance, glucose intolerance, dyslipidemia, and liver enzyme activity, without hepatic and renal damage. HBU651 ameliorated the production of inflammatory cytokines and chemokines, proinflammatory Ly6chigh monocytes, and macrophage infiltration in the blood, liver, and adipose tissue. HBU651 also decreased microglial activation in the arcuate nucleus in the hypothalamus. These findings suggest that HBU651 may be a potential candidate for the treatment of obesity-related metabolic diseases.

Polysaccharide-rich fractions from Enteromorpha prolifera improve hepatic steatosis and gut barrier integrity in high-fat diet-induced obese mice linking to modulation of gut microbiota

Polysaccharides from Enteromorpha prolifera (EP) possess important benefits in the management of obesity and associated metabolic diseases, but to date, the underlying mechanism linking this alleviative effect of EP to gut microbiota remains obscure. This study aimed to investigate the effects of EP in improving lipid metabolism disorders and intestinal barrier disruption in mice with high-fat diet (HFD), and its association with modulation of gut microbiota. C57BL/6 mice were fed a control diet or a HFD with or without 5% EP for 12 weeks. Factors related to lipid metabolism, insulin signaling and intestinal barrier integrity, as well as the involvement of gut microbiota and metabolites, were measured. EP supplementation reduced HFD-induced adiposity and mitigated insulin resistance, hepatic steatosis and elevation of serum lipopolysaccharides (LPS). HFD impaired intestinal barrier integrity while improved due to EP. Moreover, EP administration ameliorated HFD-induced gut dysbiosis, as revealed by the increased short-chain fatty acid (SCFA)-producing bacteria (e.g., Bacteroides, Parabacteroides, Alloprevotella, and Ruminococcus) and gut barrier-protective Akkermansia muciniphila and decreased endotoxin-producing bacteria (e.g., Desulfovibrionaceae and Bilophila), accompanied by enrichment in intestinal SCFA content and reduction in circulating LPS level. The change of dominant bacterial genera is significantly correlated with improved metabolic profiles and intestinal permeability induced by EP. In conclusion, our results indicate that EP can attenuate HFD-induced metabolic disorders along with restoration of gut barrier integrity and lowering of circulating endotoxin, and these improvements are associated with modulation of gut microbiota composition and related metabolites. These data deepen mechanistic understanding of the anti-obesity and metabolic improving effects of EP.

Bioactivity-based molecular networking-guided identification of guttiferone J from Garcinia cambogia as an anti-obesity candidate.

Pharmacological intervention to induce browning of white adipose tissue provides a promising anti-obesity therapy. The fruits of Garcinia cambogia (Clusiaceae) have been widely applied to manage body weight; however, the chemical principles remain unclear. The current study aims to discover browning inducers from the fruits of G.cambogia and investigate the underlying mechanisms. The bioactivity-based molecular networking and Oil Red O staining on 3T3-L1 and C3H10T1/2 adipocytes were applied for guided isolation. High-fat diet-induced obese mice were recruited to evaluate the anti-obesity activity. The bioactivity-based molecular networking-guided isolation yielded several polycyclic polyprenylated acylphloroglucinols from the fruits of G.cambogia with lipid-lowering effect in adipocytes, including guttiferone J (GOJ), garcinol and 14-deoxygarcinol. As the most potent one, GOJ (10 μM) reduced lipid accumulation by 70% and 76% in 3T3-L1 and C3H10T1/2 adipocytes, respectively. Furthermore, GOJ (2.5-10 μM) increased the expression of the deacetylase sirtuin 3 (SIRT3) and activated it, which, in turn, reduced the acetylation level of PPARγ coactivator-1α to boost mitochondrial biogenesis and promoted uncoupling protein 1 expression to enhance thermogenesis, resulting in browning of adipocytes. In high-fat diet-induced-obese mice, GOJ (10 and 20 mg·kg-1 ·day-1 for 12 weeks) protected against adiposity, hyperlipidaemia, insulin resistance and liver lipotoxicity, through boosting SIRT3-mediated browning of inguinal adipose tissue. GOJ represents a new scaffold of thermogenic inducer, which is responsible for the anti-obesity property of G.cambogia and can be further developed as a candidate for treating obesity and its related disorders.

Supplement of Caulerpa lentillifera polysaccharide by pre-prandial gavage and free feeding demonstrates differences to prevent obesity and gut microbiota disturbance in mice.

Caulerpa lentillifera has received extensive attention regarding expansion of its farming and increasing consumption. In our previous study, the structure of C.lentillifera polysaccharide (CLP) was elucidated. However, little information is available about its health effects. In this study, the anti-obesity effect of CLP was investigated by using a high-fat diet-induced obese mice model with two different supplementation methods. In vitro simulated digestion results showed that CLP significantly decreased the lipid digestibility and induced the lipid droplets aggregation in the intestinal stage to inhibit the absorption of lipids. As revealed by 16S ribosomal RNA sequencing and non-targeted metabolomics, supplement of CLP by both pre-prandial gavage and free feeding patterns effectively prevented mice obesity via ameliorating intestinal flora disturbance and regulating bile acids circulation metabolism. Of note was that CLP administration had no effect on short-chain fatty acids production, suggesting the anti-obesity effect was uncorrelated with their production. Moreover, pre-prandial administration of CLP had a better anti-obesity effect in lowering body weight and serum lipid levels, but the free feeding resulted in a higher α-diversity of gut microbiota. The findings of this study indicate that CLP could be a potential anti-obesity nutraceutical and that pre-prandial supplement of CLP may be a better intake method to exhibit its hypolipidemic effect. © 2022 Society of Chemical Industry.

Abstract 14007: Sodium-Dependent Glucose Transporters 2 Inhibition Ameliorates Obesity-Induced Metabolic Changes and Cardiomyopathy

Introduction: Inhibition of renal sodium-glucose cotransporter-2 (SGLT2) reduces urinary glucose reabsorption to decrease glycemia. Recent large-scale trials have shown that SGLT2 inhibitors provide cardio protection beyond lowering glucose. Hypothesis: Treating SGLT2 inhibitor (SGLT2i) reduces the cardiovascular risk in type 2 diabetes that indicates the potential correlation of SGLT2i in cardiomyopathy mediating metabolic effects. Methods: Male 8 weeks old C57/BL6 mice were fed high fat diet (&gt; 60% of fat) for 4 months, and treated SGLT2i, canagliflozin (CANA) in the third and the fourth month. Measured its blood glucose, body weight and echocardiology every month. Moreover, analyzed the lipid contents in its plasma, the adipose tissue, liver and heart, and also examine the cardiomyopathy markers and its potential signaling pathways. Furthermore, palmitate acid (PA) was treated to H9c2 cells to mimic a high lipid environment, and validate its potential signaling pathways. Results: Treatments of high fat diet-induced obese mice with the CANA reduced blood glucose, body weight and adiposity. Moreover, CANA reversed the obesity-induced cardiomyopathy including heart weight ratio, echocardiology and cardiomyopathy markers ( Col1 , Col4 , Icam1 and Myh7 ). Furthermore, CANA increased AKT phosphorylation which is the one of the key pathways, and reduces apoptosis in cardiomyopathy. To investigate the potential mechanisms of metabolic changes in cardiomyopathy by CANA, we searched the hepatic RNA expression from high fat diet induced obesity mice by GEO profiles online. FGF21, a hepatokine increased in CANA action by hepatic and adipose tissue lipolysis, next circulated to the heart, and induced AKT phosphorylation to reduce apoptosis. CANA increased plasma and hepatic FGF21 in obese mice. Further treating recombinant FGF21 in H9c2 differentiated cardiomyocyte like cells with palmitic acid, FGF21 reduced cardiomyocyte apoptosis via AKT phosphorylation. Conclusions: These data demonstrated that SGLT2 inhibition ameliorates metabolic changes and apoptosis via FGF21-AKT pathway in cardiomyopathy.

Abstract 12619: Diverse Effects of Cilostazol on Proprotein Convertase Subtilisin/Kexin Type 9, Obesity or Not

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis. Cilostazol exerts favorable cellular and metabolic effects; however, the effect of cilostazol on the expression of PCSK9 has not been previously reported. Hypothesis: Our study aimed to investigate the potential mechanisms of action of cilostazol on the expression of PCSK9 and lipid homeostasis. Methods: We evaluated the effects of cilostazol on the expression of PCSK9 in HepG2 cells and evaluated potential molecular mechanisms by measuring signaling molecules in the liver and serum lipid profiles in high-fat diet-induced obese mice and normal chow-fed mice. Additionally, the baseline and post-treatment serum PCSK9 levels of obese and non-obese human participants treated with cilostazol were measured. Results: Cilostazol treatment significantly induced the messenger RNA and protein expression of PCSK9 in HepG2 cells and enhanced PCSK9 promoter activity. Chromatin immunoprecipitation assays confirmed that cilostazol treatment enhanced PCSK9 transcription by binding to peroxisome proliferator-activated receptor-γ (PPARγ) via the PPARγ DNA response element. PPARγ knockdown attenuated the stimulatory effect of cilostazol on PCSK9. In vivo experiments revealed that cilostazol treatment increased serum levels of PCSK9 in normal mice but significantly reduced PCSK9 levels in obese mice (Figure). Clinical data showed that cilostazol treatment significantly reduced serum PCSK9 levels in patients with obesity. The expressions of relevant miRNAs also showed consistent results. Conclusions: The obesity-dependent effects of cilostazol on PCSK9 expression observed from bench to bedside demonstrate the therapeutic potential of cilostazol in clinical settings.

Effects of semaglutide on vascular structure and proteomics in high-fat diet-induced obese mice.

Obesity is a chronic metabolic disease caused by a combination of genetic and environmental factors. To determine whether semaglutide could improve aortic injury in obese C57BL/6J mice, and further explore its molecular mechanism of action using proteomics. 24 C57BL/6J male mice were randomly divided into normal diet group (NCD group), high-fat diet group (HFD group) and high-fat diet + semaglutide group (Sema group, semaglutide (30 nmol/kg/d) for 12 weeks). The serum samples were collected from mice to detect blood glucose, insulin and blood lipid concentrations. Aortic stiffness was detected by Doppler pulse wave velocity (PWV). Changes in vascular structure were detected by HE, masson, EVG staining and electron microscopy. The aorta-related protein expression profiles were detected by proteomic techniques, and proteins with potential molecular mechanisms were identified. Semaglutide could reduce body weight, the concentrations of blood glucose, total cholesterol (TC), triglycerides (TG), lipoprotein cholesterol (LDL-C), and reduce the aortic PWV and ameliorate vascular damage in obese mice. The results of proteomic analysis showed there were 537 up-regulated differentially expressed proteins (DEPs) and 322 down-regulated DEPs in NCD/HFD group, 251 up-regulated DEPs and 237 down-regulated proteins in HFD/Sema group. There were a total of 25 meaningful overlapping DEPs in the NCD/HFD and HFD/Sema groups. GO enrichment analysis of overlapping DEPs found that these differential proteins were mainly located in the signaling pathways of the extracellular matrix. The most obvious changes of extracellular matrix associated proteins in the three experimental groups were Coll5a1, Lama4, Sparc. Semaglutide may protect vascular structure and improve endothelial permeability by reducing the levels of Coll5a1, Lama4, Sparc in extracellular matrix, so as to improve vascular function and achieve vascular protection.

Lactobacillus delbrueckii subsp. bulgaricus strain TCI904 reduces body weight gain, modulates immune response, improves metabolism and anxiety in high fat diet-induced obese mice

The multiple probiotic characteristics of strain TCI904 isolated in this study from natural fermented milk were investigated using a mouse model. TCI904 was identified as Lactobacillus delbrueckii subsp. bulgaricu (LDB), a well-known lactic acid starter bacterium found in yogurt. TCI904 exhibited an outstanding pancreatic lipase inhibition activity among several strains of lactic acid bacteria in vitro. Its in vivo effects were further studied. In a comparison of mice fed a high-fat diet (HFD) and those fed a HFD combined with TCI904 for 9 weeks, differences were observed in various aspects of health, and the adverse effects of a HFD were prevented in the latter group. TCI904 effectively prevented fat and body weight accumulation without reducing food intake; it also modulated innate immunity and increased the level of IgA in feces, reversing the increased blood sugar and insulin levels and attenuated the hyperlipidemia caused by a HFD. Based on biochemical test data, compared with the HFD group, a HFD combined with TCI904 induced significant lowering of insulin resistance indicator, homeostasis model assessment-insulin resistance (HOMA-IR) and atherogenic indices of plasma (AIP), the atherogenic coefficient (AC) and cardiac risk ratio (CRR) and increased the cardioprotective index (CPI). In addition, the administration of TCI904 alleviated mood disorders caused by a HFD. Taking the recommended human dose of TCI904 did not affect the liver or kidney function, indicating that TCI904 has sufficient in vivo safety. Taken together, the results of the present study contributed towards validation of the probiotic benefits of lactic acid starter microflora. Orally taken TCI904 exhibited positive immune- and metabolic-modulating, and anxiolytic properties, especially in HFD-induced obesity.

Anti-obesity effect of escin: a study on high-fat diet-induced obese mice.

Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice. Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks. We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD. The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance.