Comparative acetylome analysis reveals the potential mechanism of high fat diet function in allergic disease

Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifications,and it is involved in regulating multiple body metabolic processes.This study aimed to clarify the effects of a high-fat diet(HFD)on allergy risk and the underlying mechanisms.Four-week-old male C57 BL/6 J mice were randomly divided into two groups and fed a normal fat diet(NFD)or HFD for 24 weeks.Then,serum lipids were measured,and skeletal muscle was collected for acetylome analysis.Compared with the findings in the NFD group,HFD-fed mice were obese and hyperlipidemic.Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups.Among these,eight acetylated proteins were upregulated in the HFD group.In addition,13 and 11 proteins were acetylated only in the HFD group and NFD group,respectively.These proteins were mainly involved in regulating energy metabolism and mitochondrial function.This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

The effects of the extract of oolong tea and its metabolites from Andraca theae in high fat diet induced obese Wistar rat

Obesity is a critical health issue worldwide.For a long time,the concept of drinking tea for health and pleasure is widely accepted.The strain of Andraca theae lives on the tea leaf and the bioactivity of its metabolites in the feces is unknown yet.Thus,the objective of this study was to investigate whether the extract of tea(Taiwan Tea Experiment Station No.12(TE))and its metabolites from Andraca theae(TME)could prevent obesity in the high fat diet-induced obese rats.Our results showed that TE had higher concentrations of epigallocatechin gallate(EGCG)and caffeine than that from TME.TE significantly decreased abdominal adipose tissue,especially epididymal fat via increasing preadipocyte factor 1(Pref-1),SRY(sex determining region Y)-box 9(SOX-9)and decreasing peroxisome proliferator-activated receptorγ(PPARγ),CCAAT/enhancer binding protein(C/EBP)β,C/EBPαand C/EBPβprotein expression.Taken together,these results suggest that the content of tea polyphenols in TE play an important role for alleviating abdominal fat.

Effects of Siraitia grosvenorii extracts on high fat diet-induced obese mice:a comparison with artificial sweetener aspartame

Long-term artificial sweetener intake is linked to increased risk of obesity. In the present study, supplement of natural sweetener from Siraitia grosvenorii(SG)(or Momordica grosvenorii) fruit, compared with the artificial sweetener aspartame(ASM), was evaluated for anti-obesity effects on mice fed with high fat diet(HFD). We found that, in contrary to ASM, SG extracts prevented body weight gain, the insulin resistance and fat mass accumulation in HFD mice. SG extracts treatment inhibited the infiltration of inflammatory macrophages and lowered the levels of the fat inflammatory cytokines(leptin, macrophage chemoattractant protein 1(MCP-1) and tumor necrosis factor-α(TNF-α)) in adipose tissues. In addition, SG extracts supplement counteracted the remodeling of gut microbiota resulted from HFD. However, ASM supplement aggravated the HFD-induced obese performances, fat inflammation and dysregulation of gut microbiota. Taken together, our results indicate that supplement of SG extracts may represent a promising alternation of artificial sweeteners in preventing metabolic diseases.

Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

Effects of Mogroside V on Glucose and Lipid Metabolism in High Fat Diet Mice

[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful modeling were randomly divided into normal group,model group,and MV dose group(100,200 mg/kg),with 10 mice in each group.From the ninth week,the MV dose group was given intragastric administration,and the normal group and the model group were given an equal volume of distilled water by intragastric administration for 6 weeks,then killed and blood samples and livers were collected.Serum triglycerides(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),Advanced glycation end products(AGE-P)-peptides(AGE-P)and glycosylated hemoglobin(HbA1c)content,and TG and hepatic glycogen content in liver were detected by biochemical method.Fasting blood glucose(FBG)was measured by glucose oxidase method.The fasting serum insulin(FINS)content was detected by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Oil red O staining was used to observe the fat deposition in liver tissue.[Results]MV(100,200 mg/kg)dose groups could significantly down-regulate the contents of TC,TG,LDL-C,FBG,FINS,AGE-P and HbA1c and HOMA-IR,and up-regulate HDL-C and hepatic glycogen content and reduce the fat deposits.[Conclusions]The mechanism of MV regulating glucose and lipid metabolism in mice may be related to the regulation of insulin resistance.

Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation

AIM:To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis(NASH),which has been a challenge.METHODS:In this study,we used a high fat diet(HFD)feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States.We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively,and evaluated the extent of liver damage,steatosis,and inflammasome activation.Our methods included histopathological analysis to assess liver damage and steatosis,which involved H and E and oil-red-o staining;biochemical studies to look at ALT and triglyceride levels;RNA analysis using quantitative polymerase chain reaction;and cytokine analysis,which included the enzyme-linked immunosorbent assay method to look at interleukin(IL)-1βand tumor necrosis factor-α(TNFα)levels.Furthermore,at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests(ITT)and glucose tolerance tests.RESULTS:There was no insulin resistance,steatosis,or inflammasome activation at 6 wk.In contrast,at16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male,but not female mice.In males,elevated alanine aminotransferase and triglyceride levels,indicated liver damage and steatosis,respectively.Increased liver TNFαand monocyte chemoattractant protein-1 mRNA and protein,correlated with steatohepatitis.The inflammasome components,adaptor molecule,Aim2,and NOD-like receptor 4,increased at the mRNA level,and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1βprotein levels in male mice fed a long-term HFD.Male mice on HFD had increasedα-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis.In contrast,female mice displayed only elevated triglyceride levels,steatosis,and no fibrosis.CONCLUSION:Our data indicate gender differences in NASH.Male mice fed a long-term HFD display steatohepatitis and inflammasome activation,whereas female mice have steatosis without inflammation.

Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease worldwide.However,to date,there is no ideal therapy for this disease.AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice.METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight.The control group(CON)was allowed ad libitum access to a normal chow diet.The high fat diet group(FAT)and Si-Ni-San group(SNS)were allowed ad libitum access to a high fat diet.The SNS group was intragastrically administered Si-Ni-San freeze-dried powder(5.0 g/kg)once daily,and the CON and FAT groups were intragastrically administered distilled water.After 12 wk,body weight,liver index,visceral fat index,serum alanine aminotransferase(ALT),portal lipopoly-saccharide(LPS),liver tumor necrosis factor(TNF)-αand liver triglycerides were measured.Intestinal microbiota were analyzed using a 16S r DNA sequencing technique.RESULTS Compared with the FAT group,the SNS group exhibited decreased body weight,liver index,visceral fat index,serum ALT,portal LPS,liver TNF-αand liver triglycerides(P<0.05).Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group.In particular,Oscillospira genus was a bacterial biomarker of SNS group samples.CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

Hypolipidemic Activity of Olive Oil (Olea europaea) against High Fat Diet-Induced Nonalcoholic Fatty Liver Disease (NAFLD) in Mice

Aim: The aim of the present study is to access the effect of olive oil supplementation against high fat diet induced fatty liver disease in mice. Methods: Mice were divided into five groups: Group I (normal diet), Group II (high fat diet), Group III (olive oil), Group IV and V (High Fat Diet along with olive oil). All mice were fed for 16 weeks with weight measurements every 2 weeks and then sacrificed. Biochemical analysis of blood samples was done and mice livers were histologically examined. Results: Group II mice showed significant increase in body weight as compared with Group I (p < 0.05). Group IV and V mice were significantly (p < 0.05) reduced in body weight as compared with Group II. Olive oil groups had significantly decreased triglyceride and low density lipoprotein levels as compared with Group II whereas high density lipoprotein levels were significantly increased (p < 0.05). The liver enzymes were significantly increased in Group II as compared with other groups (p < 0.05). Liver histopathology revealed drastically increased lipid droplets in Group II mice as compared with Group IV & V. Conclusion: Olive oil causes weight reduction, decreases the serum triglycerides, normalizes the liver enzymes and significantly reduces the accumulation of fat in liver. Therefore, olive oil may represent a potential therapeutic alternative for NAFLD and other fatty diseases.

Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents

Obesity has been found to be associated with increased incidence of various metabolic disorders. Anti-obesity interventions are therefore urgently needed. An earlier study has demonstrated that treatment with an herbal formula MCC, which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulate (CR) and L-carnitine (CA), reduced the weight gain in high fat diet (HFD)-fed mice. In the present study, we investigated the effect of long-term treatment with MCC (6 g/kg/day × 40 doses) and various combinations of its constituents in HFD-fed female ICR mice. Body weight change was monitored during the course of the experiment. Total and differential adiposity, plasma lipid contents, metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured. Glucose homeostasis was also assessed. Results showed that HFD increased the body weight, total and differential adiposity, and plasma lipid contents as well as impaired metabolic status in skeletal muscle and glucose homeostasis. MCC and all combinations of its constituents reduced the weight gain in HFD-fed mice, which was accompanied with an improvement on glucose homeostasis. While MC, CA and CR independently suppressed the HFD-induced weight gain in mice, MC seems to be the most effective in weight reduction, all of which correlated with the induction of mitochondrial uncoupling in skeletal muscle. Only CA and CR, but not MC, significantly reduced the total adiposity and visceral adiposity as well as plasma cholesterol level. However, the two component combinations, MC + CR and MC + CA, decreased the degree of visceral adiposity and plasma cholesterol level, respectively. MCC treatment at 1.5 g/kg (but not a higher dose of 6 g/kg) suppressed visceral adiposity and induced mitochondrial uncoupling in skeletal muscle in HFD-fed mice. The finding suggests that MCC may offer a promising prospect for ameliorating the diet-induced obesity and metabolic disorders in humans.

Effect of mango seed kernel extract on the adipogenesis in 3T3-L1 adipocytes and in rats fed a high fat diet

Mangoes (Mangifera indica L.) are one of the most important tropical foods. The seed is one of the main by-products of mango processing. Therefore, it is important to find an economically viable use for this waste (e.g., as a food additive or supplement with high nutraceutical value). We investigated the anti-obesity effects of mango seed kernel extract with hot water (MSKE-W) in 3T3-L1 adipocytes and in a high fat diet (HFD)-induced obesity rat model. MSKE-W caused a significant decrease in the activity of glycerol 2-phosphate dehydrogenase in 3T3-L1 adipocytes without eliciting cell cytotoxicity and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARγ and C/EBPα. In the animal model, rats fed an HFD containing 1% MSKE-W gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 1% MSKE-W tended to be lower than that in rats fed an HFD alone. Furthermore, histological examination of rat livers from an HFD showed steatohepatitis. However, rats on an HFD containning 1% MSKE-W showed no histopathological changes in liver tissue. Our results indicate that MSKE-W influences anti-obesity effects, both in vitro and in vivo, and suggest that MSKE-W provides a novel preventive potential against obesity.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism

BACKGROUND Studies have shown that a high-fat diet(HFD) can alter gut microbiota(GM)homeostasis and participate in lipid metabolism disorders associated with obesity.Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract(Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases.AIM To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism.METHODS Obesity was induced in rats with an HFD for 7 wk, and Sal(0.675 g/1.35 g/2.70g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors(cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNAbased microbiota analysis and untargeted lipidomic analysis(LC-MS/MS),respectively.RESULTS Sal treatment markedly reduced weight, body fat index, serum triglycerides(TG), total cholesterol(TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein(HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as c AMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs(TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs(DG14:0/22:6, DG22:6/22:6), CL(18:2/18:1/18:1/20:0), and increased ceramides(Cers;Cer d16:0/21:0, Cer d16:1/24:1),(O-acyl)-ω-hydroxy fatty acids(OAHFAs;OAHFA18:0/14:0) in the feces of rats. Spearman’s correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite.CONCLUSION Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Eating as a motivated behavior:modulatory effect of high fat diets on energy homeostasis,reward processing and neuroinflammation

Eating is a basic motivated behavior that provides fuel for the body and supports brain function.To ensure survival,the brain’s feeding circuits are tuned to monitor peripheral energy balance and promote food-seeking behavior when energy stores are low.The brain’s bias toward a positive energy state,which is necessary to ensure adequate nutrition during times of food scarcity,is evolutionarily conserved across mammalian species and is likely to drive overeating in the presence of a palatable,energy-dense diet.Animal models of diet-induced overeating have played a vital role in investigating how the drive to consume palatable food may override the homeostatic processes that serve to maintain energy balance.These animal models have provided valuable insights into the neurobiological mechanisms underlying homeostatic and non-homeostatic eating,motivation and food reward,and the development of obesity and related comorbidities.Here,we provide a brief review of this literature and discuss how diet-induced inflammation in the central nervous system impacts the neural control of food intake and regulation of body weight.The connection between diet and the immune system provides an exciting new direction for the study of ingestive behavior and the pathophysiology of obesity.

The Anti-obesity Effect of Allium cepa L. leaves on High Fat Diet Induced Obesity in Male Wistar Rats

Background:Over the years,there has been research on the anti-obesity effect of the Allium cepa bulb,but a dearth of research was carried out on the leaves,which is consumed as vegetable salad and soup,hence this study was proposed.Objective:This study aims at investigating the effect of A.cepa leaves on high fat diet(HFD)induced obesity in male Wistar rats.Methods:Twenty-eight male Wistar rats were divided into four groups with seven rats each.Apart from Group 1(normal control which received normal pelleted diet),obesity was induced in 21 rats of Group 2 to 4 with HFD.Group 2,the obese control was administered with 100%HFD,while the diet for group 3 and 4 was supplemented with 10%and 20%A.cepa powdered leaves,respectively,for 28 days.Results:In the rats treated with 10%and 20%A.cepa,body weight,fat mass,blood glucose,total cholesterol,triglycerides,aspartate amino transferase,alanine amino transferase,creatinine and urea levels were reduced significantly(P<0.05)in comparison with the obese control group.The liver of the rats treated with 10%and 20%A.cepa leaves revealed small and few amounts of fat deposits in comparison with the obese control group,which revealed numerous and large deposits of fat.The kidney of the rats treated with 10%and 20%A.cepa leaves showed moderate and mild inflammation,respectively,in comparison with the obese control group which showed acute inflammation.The leaves of A.cepa had antioxidant properties and the presence of volatile compounds with anti-obesity properties in A.cepa were identified using gas chromatography-mass spectrometry(GC-MS).Conclusion:A.cepa leaves had weight-loss effect in that it decreased body weight,fat mass,glucose and lipid levels including fat deposits in the liver.

Conditioned Place Preference Deficits in Adulthood Following High Fat and High Sugar Diet Intake in Pre- and Periadolescence: A Test of the Specificity Hypothesis

Obesity is linked to poorer cognitive performance, both of which may result from eating high-fat foods during development. In the present study, pre-and periadolescent (postnatal days 21 to 40) male rats were fed high fat (HF), high sugar (HS), or rodent chow (Chow) diets. After conditioning for 16 days with either Cheetos? (high-fat) or Froot Loops? (high-sugar) unconditioned stimuli (US) on one side of a conditioned place preference (CPP) apparatus, rats were tested on postnatal day 61 for a place preference. Chow rats preferred the US-paired side, but HF rats showed no preference. HS rats preferred the side paired with Cheetos? but not with Froot Loops?. In spite of these deficits, object recognition, a nonassociative learning task, was not impaired. These results show mixed support for the specificity hypothesis, which predicts that CPP deficits will be nutrient-specific. The results show for the first time that eating a HS diet leads to a nutrient-specific CPP deficit (for HS foods), whereas eating a HF diet leads to a general CPP deficit (for HS and HF foods).

Identification of three members of the Bmp family from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to a high fat diet

In this study,three members of the Bmp family were cloned and characterized in yellow catfish Pelteobagrus fulvidraco,including Bmp2a,Bmp4 and Bmp9.The predicted amino acid sequences of P.fulvidraco Bmp2a,Bmp4 and Bmp9 showed the characteristic domains of the Bmp family,including an N-terminal signal peptide,Arg-X-XArg site,TGF-β family signature and seven conserved cysteines,indicating that function is likely to have been conserved during evolution.mRNAs of the three Bmp genes had a variable level of expression in tissues.Compared to the control diet,a high fat diet tended to down-regulate the mRNA expression of Bmp2a,Bmp4 and Bmp9 in mesenteric fat,liver and ovary,while it tended to up-regulate their mRNA levels in muscle and kidney.The responses to dietary lipid status and the potential role in lipid metabolism have not previously been reported and reinforces the idea of their multiple functions.Our findings provide the first data about the potential role of the Bmp family in lipid metabolism in teleost.

Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats

AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.

Chlorogenic Acid Maintains Glucose Homeostasis through Modulating the Expression of SGLT-1,GLUT-2,and PLG in Different Intestinal Segments of Sprague-Dawley Rats Fed a High-Fat Diet

Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.