Mice In High Fat Diet Group Research Articles

Walnut extract protects against hepatic inflammation and toxicity induced by a high-fat diet.

A high-fat diet (HFD) is one of the main causes of obesity and metabolic diseases. The liver is particularly affected by HFD causing metabolic dysfunction associated with fatty liver disease. Therefore, different strategies are used to mitigate the negative effects of HFD. This study aimed to assess the protective effects of walnut extract against HFD-induced toxicity in mice. The mice were fed HFD and walnut extract alone or in combination. The walnut extract was analyzed for composition using high-performance liquid chromatography with a diode array detector (HPLC-DAD) and ultra-high-performance liquid chromatography with mass spectrometry (UHPLC-MS/MS). Serum lipid profile; liver histology; hepatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS), and reduced glutathione (GSH); inflammatory markers like IL-6 and TNF-α; and phospholipids were determined. Results showed that phenolic acids, epicatechin, catechin, benzaldehyde, and juglone were the main constituents in the extract. The HFD group showed increased hepatic fat accumulation as evidenced by biochemical and histopathological examinations compared to the control animals. The HFD group mice also showed increased body and cardiac weights, modified lipid profiles, decreased antioxidant status, and increased levels of hepatic inflammatory markers. The weights of the body and heart, lipid profiles, antioxidant contents (CAT, SOD, GSH-Px, TBARS, and GSH), and pro-inflammatory cytokines (IL-6 and TNF-α) were all normalized by consuming walnut extract. Similarly, the HFD group had significantly high amounts of hepatic lipase, phospholipid, and lysophospholipid levels, which were improved by walnut extract. In conclusion, walnut extract has been shown to play a unique role in promoting the recovery of liver damage caused by a high-fat diet.

Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice

Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.

Obesity, rather than high fat diet, exacerbates the outcome of influenza virus infection in influenza-sensitized mice.

Obesity is associated with impaired immune function and increased susceptibility to infection. High fat (HF) diet-induced obesity is a commonly used animal model. However, HF diet itself is known to affect immune function and infection. Thus, it is not discernable which one, HF diet or adiposity, is the major contributor to the observed impairment in immunity and susceptibility to infection in HF diet-induced obesity. We hypothesized that obesity is a major contributor to impaired immune function. Weight-matched outbred female CD-1 mice (1-mo) were randomly assigned to either a HF (45%) or a low fat (LF, 10%) diet group. Ten week after feeding their respective diets, weight gain in the mice fed the HF diet varied greatly. Thus, based on the average body weight, mice in HF diet group were divided into two sub-groups: HF lean (HF-L) and HF obese (HF-O). After 25-week, mice were immunized with an influenza A/Puerto Rico/8/34 vaccine and boosted 3-week later. Five week after the booster, mice were infected with influenza A/Puerto Rico/8/34 virus, and body weight was recorded daily for 1 month. HF-O mice exhibited significant weight loss after influenza virus challenge compared to LF and HF-L mice while LF and HF-L mice largely maintained their weight to a similar extent. Our findings suggest that obesity, rather than HF diet, per se, may impair the efficacy of influenza vaccination.

Duyun compound green tea extracts regulate bile acid metabolism on mice induced by high-fat diet.

Duyun compound green tea (DCGT) is a healthy beverage with lipid-lowering effect commonly consumed by local people, but its mechanism is not very clear. We evaluated the effect of DCGT treatment on bile acids (BA) metabolism of mice with high-fat diet (HFD) - induced hyperlipidaemia by biochemical indexes and metabolomics and preliminarily determined the potential biomarkers and metabolic pathways of hyperlipidaemia mice treated with DCGT as well as investigated its lipid-lowering mechanism. The results showed that DCGT treatment could reduce HFD - induced gain in weight and improve dyslipidaemia. In addition, a total of ten types of BA were detected, of which seven changed BA metabolites were observed in HFD group mice. After DCGT treatment, glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic acid were significantly down-regulated, while hyodeoxycholic acid, deoxycholic acid and chenodeoxycholic acid were markedly up-regulated. These results demonstrated that DCGT treatment was able to make the BA metabolites in the liver of hyperlipidaemia mice normal and alleviate hyperlipidaemia by regulating the metabolites such as glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic, as well as the BA metabolic pathway and cholesterol metabolic pathway involved.

Comparative proteomic analysis of hearts from mice with high-fat diet-induced metabolic cardiomyopathy

In patients with obesity or type 2 diabetes, the accumulation of lipotoxic by-products in cardiomyocytes leads to apoptosis and contractile dysfunction, eventually resulting in metabolic cardiomyopathy (MC). However, the underlying mechanisms remain unclear. Inb this study, a comparative proteome analysis was conducted to evaluate the differentially expressed proteins (DEPs) in the hearts of normal mice on standard diet (control group) and of high-fat diet (HFD)-induced MC mice (HFD group). We identified 90 DEPs unique to the control group and 18 DEPs unique to the HFD group. In 90 DEPs unique to the control group, only 74 DEPs were annotated in the gene ontology (GO) database. These annotated DEPs are involved in 114 biological processes, 68 molecular functions, and 174 cellular components. In 18 DEPs unique to the HFD group, only 14 DEPs were annotated in the GO database. These annotated DEPs are involved in 24 biological processes, 22 molecular functions, and six cellular components. Protein levels of two fatty acid metabolism-related enzymes, carnitine palmitoyltransferase 1B (CPT1B) and acetyl-CoA acyltransferase 2 (ACAA2), in the hearts of the mice in control group and HFD group were analyzed by immunostaining and Western blot. The results showed that the protein levels of CPT1B and ACAA2 were elevated in hearts of the mice in HFD group, which were consistent with the proteomic analysis. Our results reveal the differentially expressed proteome related to the progression of MC, providing a series of potential therapeutic targets for MC.

Mibefradil improves skeletal muscle mass, function and structure in obese mice

To observe the effect of mibefradil on skeletal muscle mass, function and structure in obese mice. Fifteen 6-week-old C57BL/6 mice were randomized equally into normal diet group (control group), high-fat diet (HFD) group and high-fat diet +mibefradil intervention group (HFD +Mibe group). The grip strength of the mice was measured using an electronic grip strength meter, and the muscle content of the hindlimb was analyzed by X-ray absorptiometry (DXA). Triglyceride (TG) and total cholesterol (TC) levels of the mice were measured with GPO-PAP method. The cross-sectional area of the muscle fibers was observed with HE staining. The changes in the level of autophagy in the muscles were detected by Western blotting and immunofluorescence assay, and the activation of the Akt/mTOR signaling pathway was detected with Western blotting. Compared with those in the control group, the mice in HFD group had a significantly greater body weight, lower relative grip strength, smaller average cross sectional area of the muscle fibers, and a lower hindlimb muscle ratio (P < 0.05). Immunofluorescence assay revealed a homogenous distribution of LC3 emitting light red fluorescence in the cytoplasm in the muscle cells in HFD group and HFD+Mibe group, while bright spots of red fluorescence were detected in HFD group. In HFD group, the muscular tissues of the mice showed an increased expression level of LC3 II protein with lowered expressions of p62 protein and phosphorylated AKT and mTOR (P < 0.05). Mibefradil treatment significantly reduced body weight of the mice, lowered the expression level of p62 protein, and increased forelimb grip strength, hindlimb muscle ratio, cross-sectional area of the muscle fibers, and the expression levels of LC3 II protein and phosphorylated AKT and mTOR (P < 0.05). Mibefradil treatment can moderate high-fat diet-induced weight gain and improve muscle mass and function in obese mice possibly by activating AKT/mTOR signal pathway to improve lipid metabolism and inhibit obesityinduced autophagy.

Therapeutic effects of myocardin-related transcription factor A (MRTF-A) knockout on experimental mice with nonalcoholic steatohepatitis induced by high-fat diet

To explore the effects of myocardin-related transcription factor A (MRTF-A) knockout on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD). Normal-fat diet (NFD) or HFD was fed to MRTF-A-knockout (MRTF-A-/-) and wild-type (WT) mice for 16 weeks. Liver histopathological status was observed using Hematoxylin and Eosin (HE) staining, Oil Red O staining, Sirius Red staining, and Immunohistochemical staining. The mRNA and protein levels in liver tissues were measured through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Compared with WT + HFD group, mice in MRTF-A-/- + HFD group were decreased in body weight, blood glucose, plasma insulin, liver TG and NAFLD activity score (NAS), with liver function recovery. Besides, compared with HFD-fed WT mice, HFD-fed MRTF-A-/- mice were improved in hepatic fibrosis, accompanied by decreased collagen content (%) and down-regulated expressions of α-SMA, COL1A2, TGFβ1, and SMAD3. In mice fed with HFD, the expression of MCP-1, CCR2, F4/80 and CD68 declined in liver tissues of MRTF-A-/- mice as compared with WT mice. Besides, in hepatic macrophages isolated from HFD-fed mice, the observed increased expression of TNF-α, IL-1β, MCP-1, as well as decreased expression of CCR2. Compared with WT + HFD group, MRTF-A-/- + HFD group mice were decreased regarding NF-κB p65 in liver tissues. MRTF-A knockout reduced macrophage infiltration, down-regulated NF-κB p65 expression, and ameliorated inflammation and fibrosis of liver tissues in mice, thereby becoming a potential therapeutic target for NASH treatment.

High-fat diet induces metabolic syndrome in mice and its influence on intestinal development, liver function and intestinal microbiota

Objective To evaluate the possibility of high-fat diet to induce metabolic syndrome and to alter intestinal development, liver function and intestinal microbiotaof C57 BL/6 J mice. Methods Total 40 of male C57 BL/6 J aged 3 weeks old were randomly divided into two groups: control group and high-fat diet group. After one week of adaptive feeding, the tested mice in high-fat diet group were fed with high-fat diet for 20 weeks, while those in control group were fed with ordinary diet. During the intervention, the body weight of the tested mice was measured weekly and fasting blood glucose(FBG) was measured monthly. Before the end of the experiment, the oral glucose tolerance test(OGTT) of the tested mice was conducted and the fecal 16 S rRNA sequencing was used to profile fecal microbiota of the test mice. Real-time qPCR was used to analyze the concentration of fecal bifidobacteria. Viscera coefficient of liver, spleen and pancreas, visceral fat-body ratio and intestinal length were measured. The indexes of liver function and the levels of serum lipids, leptin and adiponectin were also measured. Liver inflammation and fat infiltration were observed by anatomical pathological analysis. Results After intervention of high fat diet, the body weight, FBG, oral glucose tolerance, the fat-body ratio, the levels of serum lipids, leptin and adiponectin of mice were significantly increased(Pl0. 05). The inflammatory state of liver and the degree of fat infiltration increased. The length of intestine decreased(Pl0. 05). The concentration of Bifidobacterium decreased(Pl0. 05), however, the concentration of B. bifidum and B. angulatum increased(Pl0. 05). The ACE, Chao1, Shannon and Simpson indexes of the high-fat diet were significantly lower than that of the control group(Pl0. 05). Firmicutes, Proteobacteria and Deferribacteres were found significantly more in high-fat diet group(Pl0. 05), while Bacteroidetes and Verrucomicrobia were apparently more in control group(Pl0. 05). Conclusion High-fat diet could induce the metabolic syndrome in tested C57 BL/6 J, and lead to the damage of intestinal development, abnormality of liver tissue and its function, decrease diversity of intestinal microbiota, and the transformation of intestinal microbiota community to obesity type.

Arabinoxylan combined with different glucans improve lipid metabolism disorder by regulating bile acid and gut microbiota in mice fed with high-fat diet

The effect of arabinoxylan (AX) combined with β-glucan and xyloglucan on lipid metabolism by regulating bile acids and gut microbiota was investigated in mice fed with high-fat diet. Fifty male ICR/KM mice were randomly divided into five groups: control diet (CON) group, high-fat diet (HFD) group, high-fat diet with AX (HFAX) group, high-fat diet with AX and β-glucan (HFAB) group, and high-fat diet with AX and xyloglucan (HFAG) group. After 8 weeks of feeding, the mice were sacrificed and samples were collected. In contrast to CON, HFD disturbed lipid metabolism, bile acids, and gut microbiota in mice. Mice in HFD group had increase in weight, blood lipids and liver fat, and circulating bile acid as well as abnormal liver tissue morphology and disordered gut microbiota. Compared with HFD, HFAB and HFAG mice had reduced body weight and cholesterol and triglyceride levels; Fxr was activated, Cyp7a1 was inhibited to reduce bile acids, the microbial species diversity increased, the number of beneficial bacteria increased, and the number of conditional pathogenic bacteria decreased. HFAG uniquely activated intestinal bile acid receptors (Fxr and Tgr5) and increased the abundance of Bacteroidetes and Akkermansia. In summary, the effect of AX compounded glucans (β-glucan or xyloglucan) on lipid metabolism was better than that of single AX by regulating bile acid metabolism and gut microbiota possibly due to the more complex chemical structure of combined polysaccharides.

PO-034 Effect of Voluntary Exercise on Cartilage Morphology of Knee Osteoarthritis in Obese Mice Induced by High-fat Diet

Objective To examine the effect of voluntary wheel-running exercise on cartilage morphology of knee osteoarthritis(KOA) in obese mice induced by high-fat diet,and explore the protective role of 4 weeks voluntary wheel-running exercise on KOA,finally providing effective experimental evidence for clinical treatment of knee osteoarthritis.&#x0D; Methods C57BL/6J mice were randomly assigned to the C-Sed group,C-Ex group,HF-Sed group and HF-Ex group.The control groups were fed a control diet(13.5% kcal from fat),and the high-fat groups were fed a high-fat diet(60% kcal from fat).After feeding 8 weeks different diets,the exercise groups were starting running.In order to examine the effect of voluntary wheel-running exercise on cartilage morphology of KOA,the joint of knee were harvested to be fixed,decalcified and embedded in paraffin,and the four-micrometer-thick sections were stained with both HE and toluidine blue .&#x0D; Results After feeding twelve weeks different diets,the body mass of the high-fat diet group mice has a significant increase,which demonstrates that high-fat diet could successfully induce the mice obese.From the results of HE and toluidine blue,in comparison to the C-Sed group,the surface of the knee articular cartilage in the HF-Sed group was not intact and smooth,and the thickness of articular cartilage has a significant decrease（p&lt;0.001）;contrary to the HF-Sed group,the surface of the knee articular cartilage in HF-Ex group was slightly smooth,and there was significant increase in cartilage thickness.&#x0D; Conclusions Four weeks voluntary wheel-running exercise can increase cartilage thickness ,decrease the Mankin’s score and delay the degeneration of knee cartilage in obese mice.To conclude,the short-term wheel-running exercise protects against obesity-induced KOA.

Abstract 1909: Non-alcoholic steatohepatitis promotes EpCAM positive cancer stem cells mediated tumorigenesis in immunocompetent mouse model of hepatocellular carcinoma

Abstract Introduction: Non-alcoholic Steatohepatitis (NASH) is one of the major risk factors for cirrhosis and its progression to Hepatocellular Carcinoma (HCC). Cancer stem cells (CSCs) are sub-population of cells that bear stem-like properties, and are believed to contribute in tumor initiation and recurrence in tumor microenvironment. Understanding role of CSCs in tumorigenesis was limited to immunocompromised nude/SCID mouse models, and should be investigated in immunocompetent mouse model(s) representing clinical conditions. In this study, (1) we have investigated and confirmed CSCs properties in HCC cells lines, and (2) investigated tumor initiation capability of EpCAM positive CSCs in novel immunocompetent mouse model of HCC. Methods: In vitro CSC enrichment was achieved by treating murine (Hepa1-6) and human (HepG2, Hep3B) HCC cells in serum-free condition. To confirm CSCs, we analyzed CSC biomarkers (EpCAM,CD90,CD44,CD133) using flow-cytometry and Immunocytochemistry (ICC), and functional markers using Aldeflour assay and Hoechst-33342 efflux. Drug resistance property of CSCs was studied using Doxorubicin (anthracycline antibiotic) and Sorafenib (multikinase inhibitor) by MTT assay. To study in vivo tumorigenesis, immunocompetent mouse model was established using C57L/J mouse and copGFP expressing Hepa1-6 cells. Capability of EpCAM CSCs for tumor initiation was tested in 3 diet induced groups, i.e. control (10% dietary fat), high-fat (60% dietary fat), and NASH (60% dietary fat MCD diet with 0.1% methionine). 2 million FACS sorted EpCAM+/+ or EpCAM-/- cells were orthotopically injected into left liver lob. Tumor growth was monitored using high-frequency ultrasound and animals were euthanized after 18 days. Histology and ICC analysis was performed to confirm the tumors and findings. Results: Spheroid forming HCC-CSCs showed significant higher EpCAM expression and significant higher chemoresistance compared with control HCC cells. Our in vivo findings confirmed that EpCAM CSCs required NASH microenvironment. In NASH group mice, EpCAM+/+ CSCs have shown significant tumorigenesis compared with no tumors in EpCAM-/- (n=9, p&amp;lt;0.005). Histology analysis of NASH liver tissue confirmed lobular and portal inflammation, hepatocellular ballooning, and fibrosis. Control and high-fat diet group mice failed to develop tumors. Conclusions: We have developed a novel mouse model to study CSCs to overcome confounding limitations of immunocompromised mouse models for lacking functional immune system components. Our findings using immunocompetent mouse model suggest that, in HCC, (1) EpCAM+ CSCs cannot initiate tumor by itself within normal liver microenvironment in the presence of functional immune components, (2) NASH microenvironment promotes EpCAM+ CSCs mediated tumorigenesis while EpCAM-/- non-CSCs subset failed to develop tumor. Citation Format: Harshul Pandit, Yan Li, Guozhen Cui, Suping Li, Salina Li, Robert C. Martin. Non-alcoholic steatohepatitis promotes EpCAM positive cancer stem cells mediated tumorigenesis in immunocompetent mouse model of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1909. doi:10.1158/1538-7445.AM2017-1909

Effects of Capsaicin Coadministered with Eicosapentaenoic Acid on Obesity-Related Dysregulation in High-Fat-Fed Mice.

Obesity-induced inflammation contributes to the development of metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether the combination of eicosapentaenoic acid (EPA) and capsaicin could protect against high-fat diet (HFD)-induced obesity and related metabolic disorders. The experiments were performed using male C57BL/6J mice that were fed one of the following diets for 10 weeks: standard chow (5.3% fat content) (normal group), a HFD (32.0% fat content) (HFD group), or a HFD supplemented with either 4% (w/w) EPA (EPA group) or a combination of 4% (w/w) EPA and 0.01% (w/w) capsaicin (EPA+Cap group). Our results indicated that the body, fat and liver tissue weights and levels of serum glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase were significantly higher in HFD group mice than in normal group mice (p<0.05 in all cases). However, the body and fat tissue weights and serum glucose levels and homeostasis model assessment of insulin resistance were significantly lower in EPA+Cap group mice group than in HFD and EPA group mice (p<0.05 in all cases). Thus, our study suggests that the combination of EPA and capsaicin might be beneficial for delaying the progression of obesity-related metabolic dysregulation and subsequent complications.

Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary.

Obesity has a negative effect on ovarian functions, which is reported to increase the risk of infertility. The mechanism underlying obesity‑induced infertility is not yet clear. The present study established a high‑fat diet (HFD)‑induced obesity mouse model to elucidate the mechanisms underlying the effect of HFD‑induced obesity on follicular development in the mouse ovary. The 4‑week‑old female mice were fed with HFD or normal control (NC) diet for 15or 20weeks. Body mass index was used to demonstrate that the mice were obese following HFD treatment. The follicular development of the ovaries from the HFD group mice was retarded in a time‑dependent manner, as demonstrated by morphological and histological examination of the ovaries. Further investigation via western blot analysis demonstrated that the activity of the transcription factor, forkhead box O3a (FoxO3a), was increased by HFD through downregulated FoxO3a phosphorylation, which may contribute to the inhibited development of ovarian follicles. To determine the regulatory mechanism of FoxO3 on the follicular development, the expression levels of FoxO3a target protein, Smad1/5/8, were also determined and there was significant decrease in phosphorylated Smad1/5/8 in the ovaries from the HFD group compared with the NC group, indicating that FoxO3a/Smad1/5/8 may be important in the regulation of follicular development. The expression levels of the upstream regulator of FoxO3a, Akt, were also examined and it was demonstrated that Akt phosphorylation was significantly reduced in the HFD group compared with the NC group, indicating that Akt/FoxO3a may be also involved in follicular development. Together, the experiments demonstrated that HFD‑induced obesity affected the activity of the Akt/FoxO3a/Smad1/5/8 signaling pathway in a time‑dependent manner during the follicular development of the mouse ovary, leading to abnormal follicular development. These findings may provide part of a theoretical basis for the clinical prevention and treatment of obesity-associated female infertility.

High fat diet triggers cell cycle arrest and excessive apoptosis of granulosa cells during the follicular development

The regulatory mechanism of granulosa cells (GCs) proliferation during the follicular development is complicated and multifactorial, which is essential for the oocyte growth and normal ovarian functions. To investigate the role of high fat diet (HFD) on the proliferation of GCs, 4-week old female mice were fed with HFD or normal control diet (NC) for 15 weeks or 20 weeks and then detected the expression level of some regulatory molecules of cell cycle and apoptosis. The abnormal ovarian morphology was observed at 20 weeks. Further mechanistic studies indicated that HFD induced-obesity caused elevated apoptotic levels in GCs of the ovaries in a time-dependent manner. Moreover, cell cycle progress was also impacted after HFD fed. The cell cycle inhibitors, p27Kip1 and p21Cip1, were significantly induced in the ovaries from the mice in HFD group when compared with that in the ovaries from the mice in NC group. Subsequently, the expression levels of Cyclin D1, D3 and CDK4 were also significantly influenced in the ovaries from the mice fed with HFD in a time-dependent manner. The present results suggested that HFD induced-obesity may trigger cell cycle arrest and excessive apoptosis of GCs, causing the abnormal follicular development and ovarian function failure.

Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice

BackgroundObesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. MethodsSeven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11months after they had been on these diet regimens. ResultsHFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. ConclusionsThese results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition.

Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease.

This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC.

Codonopsis lanceolata extract prevents diet-induced obesity in C57BL/6 mice.

Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice.