芦笋对高脂饮食小鼠脏器指数及血生化的影响

目的 探究芦笋对高脂饮食小鼠脏器指数以及血生化的影响。方法 将实验动物随机分为正常组、高脂饮食组、高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组、高脂饮食阳性对照组。其中正常组喂食正常饲料,其余组喂食高脂饲料。分别灌胃蒸馏水（正常组、高脂饮食组）、芦笋1.05 g/（kg•d）（高脂饮食低剂量芦笋组）、芦笋2.10 g/（kg•d）（高脂饮食中剂量芦笋组）、芦笋4.20 g/（kg•d）（高脂饮食高剂量芦笋组）、降脂理肝汤1.19 g/（kg•d）（高脂饮食阳性对照组）,每天2次,每次0.35 mL。比较分析小鼠的脏器指数及血生化活性。结果 脏器方面：高脂饮食中剂量芦笋组小鼠的肝脏指数最低,但与高脂饮食组相比差异无统计学意义（P>0.05）。高脂饮食低剂量芦笋组小鼠的脾脏指数最高,并且高脂饮食低剂量芦笋组雌性与正常组雌性相比差异有统计学意义（t=1.486,P0.05）。血生化方面：高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组以及高脂饮食高剂量芦笋组小鼠的总胆固醇（TC）以及甘油三酯（TG）水平低于高脂饮食组,但与高脂饮食组相比差异无统计学意义（P>0.05）,其中高脂饮食低剂量芦笋组中的TC、TG水平最低,而高脂饮食高剂量芦笋组相应的数值最高。芦笋治疗组小鼠在高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）方面高于正常组与高脂饮食组,但差异无统计学意义（P>0.05）,其中高脂饮食低、中、高剂量芦笋三组相比,低剂量芦笋组小鼠的HDL-C数值最低,而在LDL-C方面三组差异无统计学意义。结论 高脂饮食中剂量芦笋能够降低高脂饮食小鼠的肝脏指数,高脂饮食低剂量芦笋对小鼠脾脏以及胸腺等免疫器官具有一定的促进作用,而高剂量芦笋则对小鼠脾脏以及胸腺等免疫器官具有一定的抑制作用。芦笋能降低小鼠的TC、TG水平,其中低剂量的芦笋效果最好。芦笋能提高小鼠HDL-C和LDL-C的含量。     

Effects of supplementing different chromium histidinate complexes on glucose and lipid metabolism and related protein expressions in rats fed a high-fat diet

BackgroundThe objective of this study was to investigate the effects of different chromium histidinate (CrHis) complexes added to the diet of rats fed a high-fat diet (HFD) on body weight changes, glucose and lipid metabolism parameters, and changes in biomarkers such as PPAR-γ, IRS-1, GLUTs, and NF-κB proteins.MethodsForty-two Sprague–Dawley rats were divided equally into six groups and fed either a control, an HFD, or an HFD supplemented with either CrHis1, CrHis2, CrHis3, or a combination of the CrHis complexes as CrHisM.ResultsFeeding an HFD to rats increased body weights, HOMA-IR values, fasting serum glucose, insulin, leptin, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and MDA concentrations as well as AST activities, and decreased serum and brain serotonin concentrations compared with rats fed a control diet (P < 0.0001). The levels of the PPAR-γ, IRS-1, and GLUTs in the liver and brain decreased, while NF-κB level increased, with feeding an HFD (P < 0.05). Although all the CrHis supplements reversed the negative effects of feeding an HFD (P < 0.05), the CrHis1 complex was most effective in changing the protein levels, while CrHisM was most effective in influencing certain parameters such as body weight and serum metabolites.ConclusionThe results of the present work suggest that the CrHis1 complex is most potent for alleviating the negative effects of feeding an HFD. The efficacy of CrHisM is likely due to the presence of the CrHis1 complex.     

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Cathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE^−/−) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE^−/− mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE^−/− mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE^−/− mice. In fat-induced CatE^−/− mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE^−/− mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.     

芦笋对高脂饮食小鼠体质量的影响

目的 探究芦笋对高脂饮食小鼠体质量的影响。方法 将实验动物随机分为正常组、高脂饮食组、高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组、高脂饮食阳性对照组。其中正常组喂食正常饲料,其余组喂食高脂饲料。分别灌胃蒸馏水（正常组、高脂饮食组）、芦笋1.05 g/（kg•d）（高脂饮食低剂量芦笋组）、芦笋2.10 g/（kg•d）（高脂饮食中剂量芦笋组）、芦笋4.20 g/（kg•d）（高脂饮食高剂量芦笋组）、降脂理肝汤1.19 g/（kg•d）（高脂饮食阳性对照组）,每天2次,每次0.35 mL。比较分析各组小鼠的体质量变化,同时对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比。结果 随饲养时间的增加,服用芦笋后的三组小鼠体质量均低于高脂饮食组,但与高脂饮食组相比差异无统计学意义（P>0.05）。高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组小鼠的体质量变化率低于高脂饮食组,差异无统计学意义（P>0.05）。对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比可以发现雄性小鼠的体质量变化大于雌性小鼠的,差异有统计学意义（P<0.05）。结论 芦笋能降低高脂饮食小鼠的体质量,雄性小鼠和雌性小鼠的体质量变化存在差异。     

Pivotal role of cAMP in the activation of liver glycogen breakdown in high-fat diet fed mice

Aims

Liver glycogen catabolism was evaluated in male Swiss mice fed a high-fat diet rich in saturated fatty acids (HFD) or normal fat diet (NFD) during one week.

Main methods

Liver glycogenolysis (LG) and liver glucose production (LGP) were measured either under basal or stimulated conditions (infusion of glycogenolytic agents). Thus, isolated perfused livers from HFD and NFD mice were infused with glycogenolytic agents, i.e., glucagon, epinephrine, phenylephrine, isoproterenol, adenosine-3′-5′-cyclic monophosphate (cAMP), N⁶,2′-O-dibutyryl-cAMP (DB-cAMP), 8-bromoadenosine-cAMP (8-Br-cAMP) or N⁶-monobutyryl-cAMP (N6-MB-cAMP). Moreover, glycemia and liver glycogen content were measured.

Key findings

Glycemia, liver glycogen content and basal rate of LGP and LG were not influenced by the HFD. However, LGP and LG were lower (p < 0.05) in HFD mice during the infusions of glucagon (1 nM), epinephrine (20 μM) or phenylephrine (20 μM). In contrast, the activation of LGP and LG during the infusion of isoproterenol (20 μM) was not different (HFD vs. NFD). Because glucagon showed the most prominent response, the effect of cAMP, its intracellular mediator, on LGP and LG was investigated. cAMP (150 μM) showed lower activation of LGP and LG in the HFD group. However, the activation of LGP and LG was not influenced by HFD whether DB-cAMP (3 μM), 8-Br-cAMP (3 μM) or N6-MB-cAMP (3 μM) were used.

Significance

The activation of LGP and LG depends on the intracellular availability of cAMP. It can be concluded that cAMP played a pivotal role on the activation of LG in high-fat diet fed mice.     

高脂饮食对雄性SD大鼠肠道菌群的影响

目的探讨通过膳食饲喂高脂饲料诱发的高脂血症大鼠肠道菌群结构的变化。方法 24只SD（Spra-gue Dawley,SD）雄性大鼠随机分为A、B两组,分别连续饲喂基础饲料和高脂饲料42 d,并于第0、9、18、30和42天采集大鼠粪便,应用DGGE（Denaturing gradient gel electrophoresis）和q-PCR技术对肠道菌群进行定性定量分析。结果第42天时A、B组大鼠血清总胆固醇值（TC）分别为（2.01±0.14）mmol/L、（5.16±0.22）mmol/L,B组TC水平较A组明显增高（P〈0.05）。DGGE电泳图谱显示B组42 d时肠道菌群构成较0 d时变化显著,而A组不同时期肠道菌落构成无明显差异。q-PCR定量结果显示,随着饲喂高脂饲料天数的增加,B组小鼠肠道内乳杆菌属和双歧杆菌属较0 d明显降低（P〈0.01）,而拟杆菌门数量呈递减趋势且趋势比较平缓;梭菌属呈递增趋势且增幅相对拟杆菌门的变化较大。结论高脂饮食可导致肠道菌群结构的改变,这种改变会进一步促进高脂血症的形成。     

Resistance to IP leptin-induced adipose apoptosis caused by high-fat diet in mice

The objectives of this experiment were to determine whether leptin causes adipocyte apoptosis in mice, whether peripheral administration is an effective means of studying leptin-induced adipocyte apoptosis, and whether high-fat feeding results in reduced responsiveness to leptin-induced adipocyte apoptosis. Continuous 13-day intraperitoneal infusion of 10 microg/day leptin significantly increased adipocyte apoptosis in the epididymal/parametrial fat pads of male and female mice, but only male mice developed reduced responsiveness to leptin-induced adipocyte apoptosis after high-fat (45% fat) feeding for 5 or 15 weeks. There was a positive correlation between serum leptin concentration and percent apoptotic adipocytes. These findings demonstrate that leptin administered peripherally is effective in inducing adipocyte apoptosis in mice, thus extending the possibility of studying this effect of leptin in a wider variety of animal models. In addition, high-fat feeding has a gender-specific effect on development of reduced responsiveness to leptin-induced adipocyte apoptosis.     

基于肠道菌群探讨高脂饮食在慢性便秘中的作用及机制

慢性便秘是一种患病率高、治疗困难的功能性肠道疾病。许多患者临床治疗效果差,生活质量显著降低。近年来的研究认为慢性便秘的发生发展与肠道菌群失调有关。饮食结构是影响肠道菌群组成的主要因素,已有研究发现高脂饮食可引起肠道菌群失调,进而导致慢性便秘的发生,但具体机制尚未完全阐明。本文从5-羟色胺、短链脂肪酸和慢性肠道炎症等几个方面综述高脂饮食通过影响肠道菌群引起慢性便秘的作用及机制,以期通过精准的饮食干预调节肠道菌群,达到预防和治疗慢性便秘的目的。

     

Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice

Consumption of a high-fat diet (HFD) is associated with white adipose tissue (WAT) inflammation, which contributes to key components of the metabolic syndrome, including insulin resistance (IR) and hepatic steatosis (HS). To determine the differential effects of exercise training (EX), low-fat diet (LFD), and their combination on WAT inflammation, Balb/cByJ male mice (n = 34) were fed an HFD for 12 wks before they were randomized into one of four intervention groups: HFD-EX, LFD-EX, HFD-sedentary (SED), or LFD-SED. EX mice performed 12 wks of exercise training on a motorized treadmill (1 h/d, 5 d/wk, 12 m/min, 5% grade, 65% VO₂ max), while SED mice remained sedentary in their home cages. WAT gene expression of adipokines was assessed using rt-PCR. IR was measured using HOMA-IR, and HS via hepatic triglyceride content. EX significantly reduced (53%) WAT gene expression of MCP-1, and LFD significantly reduced (50%) WAT gene expression of the macrophage specific marker, F4/80 as well as the adipocytokine IL-1ra (25%). EX independently improved IR, while both EX and LFD improved HS. These findings suggest that both diet and exercise have unique beneficial effects on WAT inflammatory markers and the mechanism by which each treatment improves metabolic complications associated with chronic consumption of an HFD may be different.     

Reduced expression of kinase-associated phosphatase in cortical dendrites of MAP2-deficient mice

We previously demonstrated that cAMP-dependent protein kinase was reduced in the dendrites of MAP2-deficient mice. In this study, we compared the expression of various protein phosphatases (PPs) between wild-type and map2(-/-) dendrites. Kinase-associated phosphatase (KAP) was the only PP which showed difference between the two phenotypes: (1) the expression of KAP was reduced in map2(-/-) cortical dendrites, and (2) the amount of KAP bound to microtubules was reduced in map2(-/-) brains. We also demonstrated in cultured neuroblastoma cells that KAP is not only expressed in dividing cells, but also in the neurites of differentiated cells. Our findings propose that KAP, which has been reported to function in cell-cycle control, has an as yet uncovered role in regulating dendritic functions. We also propose MAP2-deficient mice as an ideal system for identifying protein phosphatases essential for dendritic functions.     

Genome-wide identification and characterization of perirenal adipose tissue microRNAs in rabbits fed a high-fat diet

MicroRNAs (miRNAs) are a class of endogenous single-stranded RNA molecules that play an important role in gene regulation in animals by pairing with target gene mRNA. Extensive evidence shows that miRNAs are key players in metabolic regulation and the development of obesity. However, the systemic understanding of miRNAs in the adipogenesis of obese rabbits need further investigation. Here, seven small RNA libraries from rabbits fed either a standard normal diet (SND; n=3) or high-fat diet (HFD; n=4) were constructed and sequenced. Differentially expressed (DE) miRNAs were identified using the edgeR data analysis package from R. Software miRanda and RNAhybrid were used to predict the target genes of miRNAs. To further explore the functions of DE miRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. A total of 81449996 clean reads were obtained from the seven libraries, of which, 52 known DE miRNAs (24 up-regulated, 28 down-regulated) and 31 novel DE miRNAs (14 up-regulated, 17 down-regulated) were identified. GO enrichment analysis revealed that the DE miRNAs target genes were involved in intermediate filament cytoskeleton organization, intermediate filament-based process, and α-tubulin binding. DE miRNAs were involved in p53 signaling, linoleic acid metabolism, and other adipogenesis-related KEGG pathways. Our study further elucidates the possible functions of DE miRNAs in rabbit adipogenesis, contributing to the understanding of rabbit obesity.     

Chlorella modulates insulin signaling pathway and prevents high-fat diet-induced insulin resistance in mice

Aims

The search for natural agents that minimize obesity-associated disorders is receiving special attention. In this regard, the present study aimed to evaluate the prophylactic effect of Chlorella vulgaris (CV) on body weight, lipid profile, blood glucose and insulin signaling in liver, skeletal muscle and adipose tissue of diet-induced obese mice.

Main methods

Balb/C mice were fed either with standard rodent chow diet or high-fat diet (HFD) and received concomitant treatment with CV for 12 consecutive weeks. Triglyceride, free fatty acid, total cholesterol and fractions of cholesterol were measured using commercial assay. Insulin and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). Insulin and glucose tolerance tests were performed. The expression and phosphorylation of IRβ, IRS-1 and Akt were determined by Western blot analyses.

Key findings

Herein we demonstrate for the first time in the literature that prevention by CV of high-fat diet-induced insulin resistance in obese mice, as shown by increased glucose and insulin tolerance, is in part due to the improvement in the insulin signaling pathway at its main target tissues, by increasing the phosphorylation levels of proteins such as IR, IRS-1 and Akt. In parallel, the lower phosphorylation levels of IRS-1^ser307 were observed in obese mice. We also found that CV administration prevents high-fat diet-induced dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels.

Significance

We propose that the modulatory effect of CV treatment preventing the deleterious effects induced by high-fat diet is a good indicator for its use as a prophylactic–therapeutic agent against obesity-related complications.     

Comparative proteome analysis of splenic lymphocytes in long-term high-fat diet and dietary supplement with lipoic acid mice

The objective of this investigation was to explore possible molecular changes for role of a high-fat diet (HFD)-induced oxidative stress in splenic lymphocytes, and whether a dietary lipoic acid (LA) supplement could attenuate these changes. Male C57BL/6 mice were fed one of three diets 10 weeks and outcome measures centered on parameters of oxidative stress and lymphocytes apoptosis in spleen. Two-dimensional gel electrophoresis was used to compare the proteomes of splenic lymphocytes with three dietary groups. Differentially expressed spots whose expression altered over three fold were identified by MALDI-TOF MS. In this study, HFD resulted in oxidative stress in mice spleen, and significantly increased apoptotic percentage of splenic lymphocytes. Bioinformatic evaluation results of MALDI-TOF MS showed that 20 differentially expressed protein spots were known to be involved in many processes associated with cell function, such as cytoskeleton, energy metabolism and oxidative stress, signal transduction and cell defense. In conclusion, these results indicate that HFD-induced oxidative stress could lead to the functional decline of splenic lymphocytes, and LA supplement attenuates the alterations of protein expression to maintain the basic biological processes.     

High-fat diet induced adiposity and insulin resistance in mice lacking the myotonic dystrophy protein kinase

Myotonic dystrophy 1 (MD1) is caused by a CTG expansion in the 3′-unstranslated region of the myotonic dystrophy protein kinase (DMPK) gene. MD1 patients frequently present insulin resistance and increased visceral adiposity. We examined whether DMPK deficiency is a genetic risk factor for high-fat diet-induced adiposity and insulin resistance using the DMPK knockout mouse model. We found that high-fat fed DMPK knockout mice had significantly increased body weights, hypertrophic adipocytes and whole-body insulin resistance compared with wild-type mice. This nutrient-genome interaction should be considered by physicians given the cardiometabolic risks and sedentary lifestyle associated with MD1 patients.     

Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice

Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.     

Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin-glucan fiber improves host metabolic alterations induced by high-fat diet in mice

Recent studies have provided new evidence that alterations in the composition of the gut microbiota — known as dysbiosis — participate in the development of obesity. The aim of the present study was to investigate the ability of chitin-glucan (CG) from a fungal source to modulate both the gut microbiota and glucose and lipid metabolism in high-fat (HF) diet-induced obese mice. Supplementation of the HF diet with fungal CG (10% w/w) induced caecal enlargement with prominent changes in gut microbiota: it restored the number of bacteria from clostridial cluster XIVa including Roseburia spp., which were decreased due to HF feeding. Furthermore, CG treatment significantly decreased HF-induced body weight gain, fat mass development, fasting hyperglycemia, glucose intolerance, hepatic triglyceride accumulation and hypercholesterolemia, independently of the caloric intake. All those parameters were negatively correlated with specific bacteria of clostridial cluster XIVa, i.e., Roseburia spp. (Pearson's correlations analysis). In contrast to prebiotics that more specifically target the bifidobacteria species, CG effects on obesity appear to be independent of the incretin glucagon-like peptide 1 (GLP-1) production, since portal GLP-1 and proglucagon (its precursor) expression were not modified by the dietary intervention. In conclusion, our findings support the view that chronic consumption of CG has potential beneficial effects with respect to the development of obesity and associated metabolic diabetes and hepatic steatosis, through a mechanism related to the restoration of the composition and/or the activity of gut bacteria, namely, bacteria from clostridial cluster XIVa.     

The targeted disruption of the MYPT1 gene results in embryonic lethality

Myosin phosphatase (MP) is a major phosphatase responsible for the dephosphorylation of the regulatory light chain of myosin II. MYPT1, a target subunit of smooth and nonmuscle MP, is responsible for activation and regulation of MP. To identity the physiological roles of MP, we have generated MYPT1-deficient mice by gene targeting. The heterozygous mice showed no changes in expression levels of MYPT1 and no distinct phenotype compared to wild-type mice was observed. None of the F2 mice were homozygous for the MYPT1 deletion, indicating that the targeted disruption of the MYPT1 gene resulted in embryonic lethality. The point of embryonic lethality is before 7.5 dpc. These findings indicate that MYPT1 is essential for mouse embryogenesis.