High-fat Feeding Group Research Articles

Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway

To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms. Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting. The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats. Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Reparative effects after low-dose radiation exposure: Inhibition of atherosclerosis by reducing NETs release

ObjectiveThe cardiovascular system effects of environmental low-dose radiation exposure on radiation practitioners remain uncertain and require further investigation. The aim of this study was to initially investigate and explore the mechanisms by which low-dose radiation may contribute to atherosclerosis through a multi-omics joint comprehensive basic experiment. MethodsWe used WGCNA and differential analyses to identify shared genes and potential pathways between radiation injury and atherosclerosis sequencing datasets, as well as tissue transcriptome immune infiltration level extrapolation and single-cell transcriptome data correction using the CIBERSORT deconvolution algorithm. Animal models were constructed by combining a high-fat diet with 5 Gy γ-ray whole-body low-dose ionizing radiation. The detection of NETs release was validated by enzyme-linked immunosorbent assay. ResultsAnalysis reveals shared genes in both datasets of post-irradiation and atherosclerosis, suggesting that immune system neutrophils may be a key node connecting radiation to atherosclerosis. NETs released by neutrophil death can influence the development of atherosclerosis. Animal experiments showed that the number of neutrophils decreased (P < 0.05) and the concentration of NETs reduced after low-dose radiation compared with the control group, and the concentration of NETs significantly increased (P < 0.05) in the HF group. Endothelial plaques were significantly increased in the high-fat feed group and significantly decreased in the low-dose radiation group compared with the control group. ConclusionsLong-term low-dose ionizing radiation exposure stimulates neutrophils and inhibits their production of NETs, resulting in inhibition of atherosclerosis.

Investigation on the lipid-lowering effect and mechanism by combining turmeric with hawthorn in C57BL/6 obese mice.

Study on the hypolipidemic effect of turmeric combined with hawthorn on C57BL/6 obese mice and its possible mechanism. C57 mice were fed with 60% high-fat diet for 8 weeks to establish an obesity model, and 4 mice were slaughtered to verify whether the modeling was successful. The successful mice were divided into model group (HFD), positive group (high fat feed group [HFD]+simvastatin group [SIM]), turmeric group (HFD+TUR), hawthorn group (HFD+HAW), and para-medicine group (HFD+para-drug group [DOU]) for 4 weeks by gavage intervention. Different intervention groups had certain lipid-lowering effects, and the para-medicine group showed significant differences (p<0.05, p<0.01, p<0.001) in reducing serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic acid transaminase (ALT), glutamic acid transaminase (AST), and increasing high-density lipoprotein cholesterol. In the para-medicine group, the protein expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, platelet-reactive protein receptor 36, and CCAAT/enhancer binding protein α were significantly downregulated, and the protein expression of carnitine palmitoyl transferase1 and peroxisome proliferator-activated receptor α protein expression (p<0.01, p<0.001), thus suggesting that turmeric and hawthorn are superior to turmeric and hawthorn alone in enhancing lipid metabolism-related mechanisms. Combined effects of turmeric and hawthorn improve lipid metabolism in mice, protect the liver, and improve the protein expression of liver-related genes. This study can lay the theoretical basis for the future association of medicinal food products and the development of related weight loss products.

Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice

To investigate the effects of α7 nicotinic acetylcholine receptor (nAChR) agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice. Forty obese C57BL/6J mice were randomized into high-fat feeding group, β3-adrenoceptor agonist-treated model group, α7 nAChR agonist group, and α7 nAChR inhibitor group (n=10), with another 10 mice with normal feeding as the blank control group. White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes. The expression levels of TNF-α, IL-1β, IL-10 and TGF-β in the white adipose tissue were determined by ELISA, and the mRNA levels of iNOS, Arg1, UCP-1, PRDM-16 and PGC-1α were detected using RT-qPCR. Western blotting was performed to detect the expression levels of NF-κB P65, p-JAK2, p-STAT3 in the white adipose tissue. Compared with those in the blank control group, the mice with high-fat feeding showed significantly increased body weight, more fat vacuoles in the white adipose tissue, increased volume of lipid droplets in the adipocytes, upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β, and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins (P < 0.01). Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16, PGC-1α and UCP-1, lowered TNF-α and IL-1β expressions, increased IL-10 and TGF-β expressions, and reduced M1/M2 macrophage ratio in the white adipose tissues (P < 0.05 or 0.01). Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist, promotes transformation of M1 to M2 macrophages, reduces inflammatory response in white adipose tissue, and promote beige adipogenesis and thermogenesis in obese mice.

Effect of local unstable atherosclerotic plaque on plaque formation in the carotid artery and abdominal aorta of rabbits

To analyze the effect of local unstable atherosclerotic plaque on plaque formation in the carotid and aortic arteries of rabbits. Thirty New Zealand white rabbits were randomly divided into atherosclerosis model group, highfat diet feeding group, and normal chow feeding group (blank control group). In the model group, carotid artery balloon injury was induced after 4 weeks of high-fat diet feeding. Eight weeks later, all the rabbits were euthanized for histopathological examination of the carotid artery and abdominal aorta, and the mean intimal thickness and plaque to lumen area ratio were measured using image analysis software. Venous blood samples were collected from the rabbits for blood lipid analysis. At the ends of 4, 8 and 12 weeks, the rabbits in the model group and high-fat feeding group, but not those in the blank control group, all showed significant weight gain compared with their body weight at 0 week (P < 0.05). The mean intimal thickness was significantly greater in atherosclerosis model group than in the other two groups (P < 0.05). In atherosclerosis model group, the mean intimal thickness and plaque to lumen area ratio in the injured carotid artery were significantly greater than those in the contralateral carotid artery and abdominal aorta (P < 0.05). At the end of the 12 weeks, the levels of triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and highsensitivity C-reactive protein (CRP) were all significantly higher in the model group and high-fat feeding group than in the blank control group (P < 0.05); the levels of TG, TC, LDL-C, or HDL-C did not differ significantly between the model group and high-fat feeding group (P>0.05), but the level of CRP was significantly higher in arteriosclerosis model group (P < 0.05). Local unstable atherosclerotic plaque can increase the level of CRP and promote the formation of atherosclerotic plaques in the carotid artery and abdominal aorta in rabbits.

Effect of empagliflozin on cytoskeletal repair in the hippocampus of obese mice.

We aimed to investigate the effect of empagliflozin on hippocampal phosphorylated protein levels in obese mice. Sixteen obese mice successfully modeled on high-fat diet were randomly divided into high-fat feeding group (group H) and empagliflozin group (group H + empagliflozin, group E), eight mice in each group, and eight C57BL/6J male normal mice were selected as the control group (normal control, group C). Group E was treated with empagliflozin 10 mg/kg/d for 12 weeks, while mice in groups H and C were treated with equal amounts of saline. The spatial learning memory ability of the mice was determined by the Morris water maze experiment. Further, their body weights and serological indices were measured. Finally, total proteins were extracted from hippocampal tissues for functional analysis by the phosphorylated proteomics method. The results showed that escape latency was prolonged, retention time in the target quadrant was shortened, and the number of loop penetrations was reduced in the obese mice induced by a high-calorie diet compared with normal controls, whereas escape latency was shortened, retention time in the target quadrant was increased, and the number of loop penetrations was increased after empagliflozin treatment. Phosphoproteomics in the high-fat/control (H/C), empagliflozin/high-fat (E/H), and E/C groups showed 844, 1,552, and 1,512 differentially significant phosphorylation sites, respectively. The proteins corresponding to these differentially phosphorylated sites were mainly involved in neurodegenerative pathways and actin cytoskeleton regulation. Notably, myosin heavy chain 10 (MYH10), p21 protein-activated kinase 4 (PAK4), phosphatidylinositol 3 -phosphate 5-kinase (PIKfyve), and other differentially phosphorylated proteins were involved in actin cytoskeleton regulation. We concluded that empagliflozin protects cognitive functions by inducing serine phosphorylation in MYH10, PAK4, and PIKfyve in the hippocampal tissue of obese mice.

Camellia (Camellia oleifera Abel.) Seed Oil Regulating of Metabolic Phenotype and Alleviates Dyslipidemia in High Fat-Fed Mice through Serum Branch-Chain Amino Acids.

Camellia (Camellia oleifera Abel.) seed oil (CO) has been shown to effectively reduce the blood lipid level of its host due to its fatty acid content, but the specific molecular mechanism associated with the metabolic phenotype after digestion is not clear. Here, we further investigated the relationship between branched-chain amino acids (BCAA) and the metabolic phenotype that may exhibit the anti-dyslipidemia effect of CO on mice fed a high-fat diet for 30 day C57BL/6J male mice were allocated to three groups: the control group (Cont), the high-fat feed group (HFD), and a high-fat feed group with CO treatment (CO). A serum sample was collected to detect lipid biomarkers and BCAA concentration. Notably, Low-density lipoprotein (LDL), Total Cholesterol (TC), and Triglycerides (TG) showed a significant decrease, whereas High-density lipoprotein (HDL) increased in CO mice but not in the HFD group. The concentration of Isoleucine (Ile), leucine (Leu), and valine (Val) was similar between the Cont and CO groups compared with the HFD group, exhibiting an inhibition induced by CO in mice fed with a high-fat diet. A metabolic phenotype from serum examined by non-targeted metabolite analysis using UHPLC/MS showed most metabolites exhibited lipid and BCAA metabolism. The results indicated that CO treatment notably regulated the metabolism of arachidonic acid and steroid biosynthesis in response to HFD-induced dyslipidemia. In addition, the expression of PPARγ genes that correlated with the BCAA and serum lipid biomarkers were compared, and significant inhibition was noticed, which might lead to the potential exposure of the anti-dyslipidemia mechanism of CO in HFD-fed mice. In conclusion, the expression of PPARγ genes, serum lipid level, BCAA concentration, and the metabolic phenotype was significantly positive in correlation with a high-fat diet, whereas oral CO improved the biomarkers and metabolism of some specific serum metabolites in HFD-fed mice.

Chylous ascites with lymphatic leakage localization: technical aspects and clinical applications.

BackgroundCarbon nanoparticle suspension (CNS) was applied to locate the lymphatic leakage in chylous ascites (CA). However, the flow speed and distance of the CNS were particularly decreased in the following two cases (patient 5 and 6). This study aimed to investigate and improve the flow speed and distance of the CNS via a rat model.MethodsSeven patients with CA were accepted for surgery in the past two years. Clinical data were recorded. Rats were divided into two groups to confirm the hypothesis regarding whether accepting milk or orally administered food before surgery was the key factor in CA surgery with CNS. The animals were divided into 2 groups: experimental group of 5 rats receiving fat emulsion injection (2 g/kg) 30 min before the operation and control group of 5 rats receiving saline. We analyzed flow speed and distance of the CNS in two groups of rats. The hypothesis established was that CNS movements pattern differ depending on the degree of capillary lymph duct filling. Finally, the late case reconfirmed the hypothesis again.ResultsIn animal experiments, the CNS in the preoperative high-fat feeding group moved faster and over a longer distance than that in the control group (0.51 ± 0.09 cm vs. 0.19 ± 0.10 cm, respectively; p < 0.05). Based on this, the CNS was applied to the seventh patient, who had been given a diet with a slightly higher fat content 3 days before the operation, and marked improvement with a complete cure was recorded.ConclusionsThe capillary lymph duct was beginning to swell after dietary intake. The dilation of the lymph vessel could make it easier for the CNS to move and reach the leakage.Supplementary informationThe online version contains supplementary material available at 10.1186/s12893-022-01619-7.

Effects of Potentilla Anserina Polysaccharide Combined with Aerobic Exercise on Blood Lipid Level and the Liver in Experimental Hyperlipidemia Rats

Objective: To study the effects of potentilla anserina polysaccharide combined with aerobic exercise on blood lipid level and the liver in experimental hyperlipidemia rats. Methods: 50 healthy male wistar rats were selected after 5 days adaptive feeding. Rats were randomly divided into basic feeding group and high fat feeding group, which were divided into hyperlipidemia group (H group), hyperlipidemia + potentilla anserina polysaccharide group (P group), hyperlipidemia + aerobic group (E group), hyperlipidemia + potentilla anserina polysaccharide + aerobic group (PE group), 10 for each group, and basic feeding group were 10 for normal control group (C group). The feeding method of C group , H group and E group intragastrically treated with normal saline (8ml/kg), P group and PE group with potentilla anserina polysaccharide at the dose of 100mg /( kg·d). Once a day, for 10 weeks . Group E and PE for platform sports, 16 m/min, the slope is 0°, 15 min/d, increased the time every day to 60 min/d for a week at last. 5° in the second week, 60 min/d, 18 m/min, with the same running intensity amount to 50% maximum oxygen intake. Fifty healthy male wistar rats were selected after 5 days of adaptive feeding. Rats were randomly divided into basic feed and hyperlipidemia feed feeding, divided into hyperlipidemia (H group), hyperlipidemia + potentilla anserina polysaccharide (P group), hyperlipidemia + aerobic (E group), hyperlipidemia + potentilla anserina polysaccharide + (PE group), 10 each group and basic feed feeding in normal control (C). The feeding method provided C with gastric saline (8 ml/kg) and H, P and PE groups with potentilla anserina polysaccharide (8ml/kg, PAP solution of 100 mg/kg), once a day for 10 weeks. Group E and PE for rat platform training, 16 m/min, 0°, 15 min/d, per day, 5° in the second week, 60 min/d, 18 m/min, with the same running intensity and 50% maximum oxygen intake. Once a day, 6 days a week running as aerobic exercise, and test each indicator after 10 consecutive weeks. Measure the serum triglyceride (TG) , total cholesterol (TC ), low density lipoprotein(LDL) , high density lipoprotein (HDL), glutamate pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), The malondialdehyde (MDA) and superoxidase dismutase (SOD), levels of the liver tissue were measured. Results: Compared with the C group, extremely significantly differences in serum TC, LDL, ALT, SOD in H, P, and E groups (p<0.01), extremely significantly differences in serum TG, HDL, AST and MDA in H group (p<0.01), significant difference in HDL in the P and E groups (p<0.01, p<0.05). However, there were no significant differences from each item in the PE group compared with C group (p>0.05). Compared with the H group, the serum TC, TG, LDL, HDL, ALT, SOD and MDA are very significant difference in C, H, P, E, and PE groups (p<0.01). Compared with the PE group, very significant differences in the serum TC, LDL and SOD in H, P, and E group (p<0.01). The serum TG, HDL, ALT, AST and MDA associated with the H group also has extremely significant differences compared with the PE group (p<0.01). The HDL associated with the E group, the AST in the P group, there were significant differences compared with the PE group (p <0.05). Conclusion: PAP, hyperlipidemia in rats with PAP and elevated SOD, has an obvious effect in reducing the symptoms of hyperlipidemia, but gastric PAP combined with aerobic exercise reduced the symptoms most significantly in hyperlipidemia rats, after 10 weeks of gastric PAP and aerobic exercise, hyperlipidemia rats compared with ordinary feed-fed control group, has the best effect p>0.05.

Switching from high-fat feeding (HFD) to regular diet improves metabolic and behavioral impairments in middle-aged female mice

Obesity represents a risk factor for metabolic syndrome and cardiovascular and psychiatric disorders. Excessive caloric intake, particularly in dietary fats, is an environmental factor that contributes to obesity development. Thus, the observation that switching from long-standing dietary obesity to standard diet (SD) can ameliorate the high-fat diet-induced metabolic, memory, and emotionality-related impairments are particularly important. Herein we investigated whether switching from the high-fat diet (HFD) to SD could improve the metabolic and behavioral impairments observed in middle-aged females C57Bl/6 mice. During twelve weeks, the animals received a high-fat diet (61 % fat) or SD diet. After 12-weeks, the HFD group’s diet was switched to SD for an additional four weeks. It was observed a progressive deleterious effect of HFD in metabolic and behavioral parameters in mice. After four weeks of HFD-feeding, the animals showed glucose intolerance and increased locomotor activity. A subsequent increase in the body mass gain, hyperglycemia, and depressive-like behavior was observed after eight weeks, and memory impairments after twelve weeks. After replacing the HFD to SD, it was observed an improvement of metabolic (loss of body mass, normal plasma glucose levels, and glucose tolerance) and behavioral (absence of memory and emotional alterations) parameters. These results demonstrate the temporal development of metabolic and behavioral impairments following HFD in middle-age female mice and provide new evidence that these alterations can be improved by switching back the diet to SD.

Protective effects of Gymnaster koraiensis extract on high fat diet-induced fatty liver in mice

Obesity produces non-alcoholic liver disease, with relationship of the beginning of abnormal lipid metabolism. Recent studies show that abnormal cholesterol metabolism has a specific role in the pathological cause of non-alcoholic fatty liver disease (NAFLD). Gymnaster koraiensis (GK), a worthy perennial Korean wild plant has specific polyacetylene compounds. Many researches have presented that GK has many pharmacological properties, such as oxidation prevention, liver protection, and inflammation prevention. However, the conservative effect of GK on non-alcoholic fatty liver has not been researched so far. Male C57/BL6J mice were randomly separated to normal feeding (ND) (fed a ND for 12 weeks) and high fat feeding (HF) groups. Mice in the HF group were administered a high fat feeding (60% kcal high fat diet) and administered GK extract (125, 250, or 500 mg/kg/day), silymarin (200 mg/kg/day), or no treatment for 12 weeks. Each treatment group contained eight mice. The administration with GK decreased serum levels of triglycerides, total cholesterol, LDL-cholesterol, alanine aminotransferase and aspartate aminotransferase, while decreased body weight, body fat and liver weight. Alterations in liver histology, as assessed by H&E and Oil-red O staining, showed that the GK treatment decreased amass of lipids and NAFLD activity scores in liver. These results present that GK extract may be potential therapeutic agent for NAFLD by preventing increases of serum lipids and increases of body weight and fat, while decreasing lipid accumulation and increase of liver weight in high fat diet-triggered fatty liver.

PO-235 Endurance training increased the expression of myocardin in thoracic aorta of T2DM rats

Objective In recent years, a large number of experimental studies have shown that the proliferation and migration of VSMC are the pathological basis of various vascular diseases, including AS, hypertension, and restenosis after angioplasty. It’s rather remarkable that Phenotypic Modulation of VSMC plays an important role in their proliferation and migration. Myocardin is a key transcription factor for the differentiation of VSMC by far, which can effectively activate the differentiation process of SMC. Many studies have shown that endurance training is an effective way to improve glucose and lipid metabolism. This study attempted to explore the effects of long-term external stress (endurance training) on arterial smooth muscle phenotype modulation and myocardin through secondary vascular disease, in order to provide theoretical support and practical basis for sports therapy in T2DM secondary diseases.&#x0D; Methods Male SD rats were randomly divided into the general feed group (pC) and the high-sugar and high-fat feed group (pD). After 7 weeks, rats in pD were injected a small doses of streptozotocin through abdominal cavity. Those Non-fasting Blood Glucose (NFBG) ≥16.7mmol/L after 72h and with insulin resistance were diagnosed as diabetes. Thereafter, the pC group was randomly divided into a blank control group (C), an endurance training group (E), a diabetes model group (D), and a diabetic+endurance training group (DE). No load platform training was conducted in E&amp;DE group, 5 days per week for 8 weeks. 8 weeks after, BP was measured through left common carotid artery intubation, blood sugar was test by enzyme chemical assay, α-SM-actin, SM-MHC , SM22α,Myocardin and KLF4 were measured through ELISA. &#x0D; Results 1. Compared with C, MCP (carotid blood pressure) of D increased significantly, FBG and FINS decreased significantly, expression of α-SM-actin, SM-MHC, SM22α and Myocardin Significantly dropped, KLF4 rose significantly. Compared with D, the expression of FBG in E was significantly down-regulated, FINS was significantly up-regulated, and the expression of α-SM-actin, SM22α and Myocardin was significantly up-regulated.&#x0D; Conclusions 8 weeks of endurance training significantly increased the expression level of contractile protein in the aorta smooth muscle of diabetic rats, making the smooth muscle phenotype changed from synthetic to contractile type, which effectively inhibited the excessive proliferation and migration of smooth muscle cells.Myocardin is one of the hot spots in the study of vascular differentiation in recent years. This study shows that the role of endurance training in improving plaque formation and lowering blood pressure may be produced by regulating myocardin.

Effects of high-fat feeding on growth and expression of IGF-1 and IRS-1 in adolescent rats

Objective To observe the effects of high-fat feeding on growth and the expression of insulin-like growth factor 1(IGF-1), insulin receptor substrate 1(IRS-1) in adolescent rats' liver with non-alcoholic fatty liver disease, and to elucidate the relationship between growth failure in adolescent rats with non-alcoholic fatty liver disease and IGF-1, IRS-1 turbulence. Methods Thirty-six Sprague-Dawley (SD) young rats of 21 days were randomly divided into normal control group(NC group, n=18) and high-fat feeding group(HF group, n=18). Non-alcoholic fatty liver disease(NAFLD) model was induced by feeding the SD rats with high-fat food.Immunohistochemistry was applied to detect the expression levels of IGF-1 and IRS-1 in liver tissue.The expressions of mRNA of IGF-1 and IRS-1 were measured by RT-PCR. Results Compared with NC group, the serum alanine amino transferase(ALT), total cholesterol(TC), triglyceride(TG) of HF group in the 6th, 8th, 12th week were gradually increased.The serum ALT[(194.67±11.15)U/L], TC[(1.81±0.09)mmol/L], TG[(0.34±0.05)mmol/L]contents of HF group at 8th week were higher than those at 6th week[(166.00±22.01)U/L, (1.52±0.22)mmol/L, (0.41±0.12)mmol/L, respectively], and the serum ALT[(213.0±27.67)U/L], TC[(2.15±0.37)mmol/L], TG[(0.38±0.15)mmol/L]contents of the 12th week were significantly increased compared with 6th week and 8th week.The constitution and body length of the HF group were lower than those of the normal control group.With time extended, the liver tissue steatosis, inflammation, the balloon like change of the liver tissue pathology of HF group in 6, 8, 12th week gradually increased.Immunohistochemistry results showed that HF group IRS-1[(1.46±0.23), (0.74±0.17), (0.85±0.31)], IGF-1[(0.92±0.02), (0.83±0.02), (0.77±0.03)]expression gradually decreased, the difference was statistically significant(F=36.024, P<0.05). IGF-1 and IRS-1 mRNA expressions in HF group were consistent. Conclusion The liver tissue IGF-1 and IRS-1 are correlated with the weight and body length.The growth failure of young rats induced by high-fat feeding may be related to the decreased expression of IGF-1 and IRS-1. Key words: Fatty liver; Dietary fats, unsaturated; Insulin-like growth factor 1; Insulin receptor substrate proteins

Histologic and Metabolic Derangement in High-Fat, High-Fructose, and Combination Diet Animal Models.

Background. We used high-fat (HF), high-fructose (HFr), and combination diets to create a dietary animal model of nonalcoholic fatty liver disease (NAFLD). Comparison of both clinical phenotypes has not been well defined. The purpose of this study was to compare histologic and metabolic characteristics between diets in an animal model of NAFLD. Methods. NAFLD was induced in rats by feeding them HF, HFr, and combination (HF + HFr) diets for 20 weeks. The degree of intrahepatic fat accumulation, inflammation, and oxidative stress was evaluated. Metabolic derangements were assessed by the oral glucose tolerance test and the intrahepatic insulin signal pathway. Results. Body weight gain and intrahepatic fat accumulation were more prominent in the HF feeding group than in the HFr group. The expressions of NOX-4 and TLR-4 were higher in the HF and HFr combination groups than in the HF-only group. Other intrahepatic inflammatory markers, MCP-1, TNF-α, and endoplasmic reticulum stress markers, were the highest in the HF + HFr combination group. Although intrahepatic fat deposition was less prominent in the HFr diet model, intrahepatic inflammation was noted. Conclusions. Intrahepatic inflammation and metabolic derangements were more prominent in the HF and HFr combination model than in the HF monodiet model.

Indução de Diabetes Tipo 2 por dieta hiperlipídica e baixa dose de estreptozotocina em ratas wistar

O objetivo do presente estudo experimental foi desenvolver um modelo animal de diabetes tipo 2 que mimetizasse o curso natural e metabólico desta doença em humanos. Assim, foi oferecida uma dieta hiperlipídica (com aproximadamente 60% das calorias totais provenientes de lipídeos) por três semanas, estabelecendo então, um quadro de resistência à insulina. Em seguida, as ratas foram submetidas a uma dose única de estreptozotocina (STZ) (35mg/kg de peso corporal) em veículo de tampão citrato (pH: 4,4). Após 1 semana da injeção de STZ, as ratas foram submetidas ao teste oral de tolerância à glicose, mediante administração oral de glicose (2g glicose/kg de massa corporal). Os dados foram submetidos à comparação entre os grupos utilizando-se o teste t. A significância em todos os testes se deu ao nível de p ≤ 0,05. O grupo controle manteve a concentração média de glicose final igual a inicial. Após ingestão da dieta hiperlipídica houve um aumento da glicemia de jejum em cerca de 16,5% em relação ao momento inicial do experimento (P&lt;0,0001) enquanto os animais que receberam a dieta controle apresentaram um aumento aproximado de 8,7%. Uma semana após a administração intraperitoneal de STZ, pode-se verificar aumento da concentração média de glicose no grupo hiperlipídico em cerca de 194,2%, representando um aumento de 275,8% (P&lt;0,0001) quando comparado ao GC. O presente estudo retrata que a combinação de uma dieta hiperlipídica e baixa dose de estreptozotocina serve como um modelo animal alternativo para a diabetes tipo 2 simulando a síndrome em humanos.

Pengaruh Air Perasan Umbi Bawang Merah (Allium ascalonicum L.) terhadap Malondialdehid (MDA) Plasma Mencit yang diinduksi Hiperkolesterolemia

Malondialdehyde, a product of lipid peroxidation, is often used as an indicator to detect the oxidative stress damaged in the body. Lipidperoxidation is associated with progression of atherosclerosis. It is known that onion (Allium ascalonicum L.) can be used as an antioxidantand hypolipidemic agent, but whether onion can decrease hypercolesterolemia mice MDA plasma induced by yolk is still unknown. Thepurpose of this study was to investigate the effect of onion’s juice on hypercolesterolemia mice MDA plasma level. This was an experimentallaboratory research with post test only design with control. The measured parameters were cholesterol and MDA level on tested groups.Groups with treatment consist of yolks group, and 80% shallot juice, simvastatin and aquadest were separately used as positive and negativecontrol. The result showed that there was significant difference between high fat feed group which added 80% onion’s juice and high fat feedgroup only. Addition of 80% onion’s juice in high fat feed groups decreased MDA plasma level equal to normal feed group. In conclusion, itwas proved that onion’s juice decreased mice MDA plasma level.

Paradoxical reduction in cardiac O‐GlcNAcylation following short‐term high fat feeding

Chronic high fat feeding (HFF) leads to hyperglycemia which elevates cardiac O‐linked B‐N‐acetylglucosamine glycosylation (O‐GlcNAcylation) of mitochondrial proteins and leads to reduced oxidative phosphorylation. This impairs the hearts ability to oxidize surplus fatty acids perpetuating substrate toxicity associated with lipid excess. We evaluated short‐term HFF on C57BL/6 cardiac O‐GlcNAcylation and mitochondrial function. Following 20 wk HFF, mice were obese (49.12 +/− 0.73 vs. 31.82 +/− 0.95 mg; n=10), but had similar fasting blood glucose (13.98 +/− 1.45 vs. 16.56 +/− 0.91 mM; n=10). High‐resolution respirometry exhibited increased state 3 oxygen consumption supported by complex I substrates in HFF permeabilized cardiac fibers (288.82 +/− 24.81 vs. 188.80 +/− 16.48 pmol/s/mgww; n=8). This was associated with ~1.5‐fold greater mitochondrial density in the HFF group as determined by electron microscopy (n=5). Additionally, global O‐GlcNAcylation decreased ~7‐fold in the HFF mice (n=6) and immunoprecipitation experiments show complex I subunit NDUFA9 O‐GlcNAcylation is reduced ~2.5‐fold (n=6). In conclusion, prior to the onset of hyperglycemia, cardiac mitochondrial oxidative phosphorylation increases to accommodate excess substrate availability due, in part, to enhanced mitochondrial density and decreased O‐GlcNAcylated NDUFA9. This work was supported by CIHR, AHFMR, CDA and HSF.

The role of rice bran extract on acetyl CoA carboxylase in liver of rats fed a high-fat diet

Rice bran water extract (RBE) was shown to reduce fat mass in rats fed a high-fat diet [1]. The involvement of RBE in metabolic alteration were investigated in 7 groups of Sprague Dawley rats, 8 rats each. High-fat fed group 3 to 7 were either co-treated daily with RBE (220.5, 2205, 4410mg/kg) or metformin (19.10, 38.20mg/kg). Oral glucose tolerance was tested at the end of forth week. Rats were killed and specimens were collected. The results showed that the mean±SEM of abdominal fat weight, epididymal fat cell size and triglyceride level in blood and liver were increased whereas cholesterol in high-density lipoprotein was decreased in rats fed a high-fat diet alone as compared to rats fed with chow (7.65±0.29 vs. 4.73±0.39g.; 4919.76±453.59 vs. 2835.23 ±249.15µm2; 44.67±2.72 vs. 35.00±2.02mg/dL; 2.50±0.26 vs. 1.48±0.08mg/mL; 67.14±1.62 vs. 77.20±2.82mg/dL, respectively). At least 2205mg RBE/kg or 19.10mg metformin/kg were able to significantly reduce abdominal fat weight and triglyceride levels in liver. ACC activity was increased in high-fat feeding group but the activities retuned to normal when they were also received RBE or metformin, though there was no statistic significance. In conclusion, fatty acid flux might induce fat synthesis in liver as an initial step in increasing fat accumulation [2]. Both RBE and metformin were able to reduce the alteration.

석이버섯과 운지버섯 균사체 추출물이 장내 세균의 생육에 미치는 영향

본 연구에서는 비만과 관련된 요소 중 하나인 장내 균총을 개선하고자, 식이섬유소가 풍부하고 저칼로리인 담자균류 추출물을 이용하여 in vitro 상에서 비만 관련 장내 미생물에 대한 항균활성을 조사하였다. 항균성 담자 균류 소재 탐색결과 석이버섯 자실체와 운지버섯 균사체의 추출물을 선발하였고, 선발된 담자균류 소재 추출물의 특성을 분석한 결과 열에 대단히 안정하였고, pH에도 비교적 안정한 것으로 나타났다. 또한 rat을 이용한 동물실험에서 석이버섯 80% 에탄올 추출물 투여군이 고지방식이만 투여한 군에 비하여, 장내 균총에서 Bifidobacterium spp.가 증가되었고, Clostridium spp.와 Eubacterium spp.는 감소된 것으로 나타났다. 석이버섯과 운지버섯 추출물이 첨가된 기능성 음료를 제조하고자 관능평가를 실시한 결과, 운지버섯 균사체 배양액에 석이버섯 추출물을 3% 첨가한 실험구가 가장 좋은 평가를 받았다. 이러한 결과를 토대로 석이버섯과 운지버섯 추출물이 장내 균총 개선을 위한 기능성 식품소재로 활용될 수 있을 것으로 생각된다.

Effects of calorie restriction on SIRT1 expression in liver of nonalcoholic fatty liver disease: experiment with rats

To investigate the molecular mechanisms of calorie restriction (CR) in treatment of nonalcoholic fatty liver disease (NAFLD). 25 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n = 7) fed with regular diet and high fat diet-NAFLD model group (HFM, n = 18) fed with high-fat diet. Two months later, the rats in Group HFM were further divided into 2 subgroups: continuous high-fat feeding group (HF, n = 9) and normal diet feeding with 60% calorie restriction group (CR, n = 9). The rats were sacrificed after 1 month calorie restriction. By the end of experiment, body weight (BW), visceral fat mass (VF), fasting plasma glucose (FPG), fasting serum insulin (FINS), blood lipids (BL), including total cholesterol (TC) and triglyceride (TG), and hepatoultrastructure changes were examined to evaluate the effect of different feeding protocols on the experimental animals. The mRNA expression of the longevity gene SIRT1 in the liver was detected by RT-PCR. Western blot analysis was performed to determine the expression of SIRT1 protein in each group. Electron microscopy showed that the rats in group HF displayed obviously abnormal hepatoultrastructure, and the ultramicropathology changes of liver cell were improved obviously in Group CR. The VF, FINS, FPG, TC, and TG of the Group HF were 15.1 g +/- 4.1 g, 29.22 mU/L +/- 7.28 mU/L, 6.2 mmol/L +/- 1.46 mmol/L, 2.61 mmol/L +/- 0.29 mmol/L, and 1.35 mmol/L +/- 0.21 mmol/L respectively, all significantly higher than those in Group NC (9.0 g +/- 0.4 g, 13.09 mU/L +/- 1.18 mU/L, 4.4 mmol/L +/- 0.57 mmol/L, 1.41 mmol/L +/- 0.28 mmol/L, and 0.67 mmol/L +/- 0.10 mmol/L respectively, all P < 0.01). The mRNA expression of SIRT1 in the liver of Group HF was significantly lower than that of Group NC (P < 0.05), and the mRNA expression of SIRT1 in the liver of Group CR was significantly higher than those of Group HF and Group NC (both P < 0.01). The protein expression of SIRT1 of Group HF was significantly lower than that of Group NC (P < 0.01), and that of Group CR was significantly higher than that of Group HF, however, still significantly lower than that of Group NC (both P < 0.01). The BW and VF, FINS, FPG, TC, and TG of Group CR were all significantly lower than those of Group HF (all P < 0.01). CR can reverse NAFLD significantly. The increased expression of SIRT1 in liver induced by CR may be an important molecular mechanism involved in the improvement of NAFLD by CR.