High-fat Group Research Articles

Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis.

Pharmacological treatment modalities for non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are scarce, and discoveries are challenged by lack of predictive animal models adequately reflecting severe human disease stages and co-morbidities such as obesity and type 2 diabetes. To mimic human NAFLD/NASH etiology, many preclinical models rely on specific dietary components, though metabolism may differ considerably between species, potentially affecting outcomes and limiting comparability between studies. Consequently, understanding the physiological effects of dietary components is critical for high translational validity. This study investigated the effects of high fat, cholesterol, and carbohydrate sources on NASH development and metabolic outcomes in guinea pigs. Diet groups (n = 8/group) included: low-fat low-starch (LF-LSt), low-fat high-starch (LF-HSt), high-fat (HF) or HF with 4.2%, or 8.4% sugar water supplementation. The results showed that caloric compensation in HF animals supplied with sugar water led to reduced feed intake and a milder NASH phenotype compared to HF. The HF group displayed advanced NASH, weight gain and glucose intolerance compared to LF-LSt animals, but not LF-HSt, indicating an undesirable effect of starch in the control diet. Our findings support the HF guinea pig as a model of advanced NASH and highlights the importance in considering carbohydrate sources in preclinical studies of NAFLD.

Metabolic Changes in Hyperlipidemic Rats After The Administration of Xuezhikang

Background: Xuezhikang capsule, which contains cholesterol synthase inhibitors and a large number of natural statins, is put in the clinical application of lipid-lowering and so on. However, the specific use of dose, lipid-lowering effect and the relationship between metabolites are to be further studied. Introduction: Metabonomics is the study of the relationship between the change of quantity and physiological changes from metabolites. At present metabolomics has been widely used in drug development and testing. In this study, we developed a metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to find out hyperlipemia-related substances, and study the lipid-lowering mechanism of Xuezhikang. Method: Fifty SD rats (220 ± 20 g) were given high-fat diet. After four-weeks modeling, they were randomly divided into semi-control group, high fat group, simvastatin intervention group and Xuezhikang intervention group (0.23, 0.69, 1.15 mg/kg, low, medium, high), each dosage in eight rats. The control group (rest eight rats) were given normal diet, and no specific treatment. The rats were sacrificed at the end of the experiment. Result: The biochemical and body weight indexes of the normal control group and the high fat group were significantly different (P <0.05), which indicated that the model of hyperlipidemia was established success. There was significant difference (P <0.05) between Xuezhikang intervention group and high fat control group (P <0.05), and hyperlipemia metabolomics related markers, oxalic acid, butyric acid, mannitol, glucose, glucuronic acid were found. Glucuronic acid and non-binding bilirubin combined with bilirubin, combined with some of the liver harmful substances, play a detoxification effect. Conclusion: The results of metabonomics showed that the high-fat group and the control group have significant differences. Mannose, glucose content is relatively stable, lipid metabolism in high-fat group stearic acid, palmitic acid levels decreased, suggesting that high-fat diet disorders rat body lipid metabolism. It is worth mentioning that the experimental evaluation of rats, such as biochemical indicators and pathological results are prompted to model success, Xuezhikang intervention effect is more significant, consistent with the expected. Conclusion: The results of metabonomics showed that the high fat group and the control group were significant difference. Mannose, glucose content is relatively stable, lipid metabolism in high-fat group stearic acid, palmitic acid levels decreased, suggesting that high-fat diet disorders rat body lipid metabolism. It is worth mentioning that the experimental evaluation of rats such as biochemical indicators and pathological results are prompted to model success, Xuezhikang intervention effect is more significant, consistent with the expected.

Buchholzia coriacea seed (wonderful kolanut) alleviates insulin resistance, steatosis, inflammation and oxidative stress in high fat diet model of fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic condition with multiple pathological features and it currently has no specific treatment or approved drug. Wonderful kolanut widely consumed fresh or cooked has been applied in the treatment of numerous diseases in folk medicine. In this study, we evaluate the therapeutic potentials of hydroethanolic extract of defatted Buccholzia coriacea seeds (HEBCS) in NAFLD model. HEBCS was subjected to liquid chromatography - mass spectrometry, and 30 male BALB/c mice (28±2g) were allocated to three (3) experimental groups (n=10/group). Mice in group I were fed chow diet (CD); those in group II, high fat diet (HFD) and group III, HFD and 250mg/kg HEBCS p.o. daily for six weeks. HEBCS alleviates HFD-induced insulin resistance and high plasma insulin and glucose levels. It further alleviates hepatic steatosis, and alters plasma lipid profile. HEBCS also protected against HFD-induced inflammation, oxidative stress and hepatocellular damage. In conclusion, HEBCS alleviated NAFLD in mice via suppression of insulin resistance, hyperlipidemia, inflammation and oxidative stress. PRACTICAL APPLICATIONS: Bioactive polyphenols and alkaloids were identified in hydroethanolic extract of defatted Buccholzia coriacea seeds (HEBCS). This study projects HEBCS as a potential therapeutic agent in the treatment of NAFLD. NAFLD is a multi-factorial condition and therefore, HEBCS is promising considering its multiple-target actions in the current model of NAFLD. HEBCS alleviates insulin resistance, metabolic dysfunction, steatosis, and inflammation in this model. There is a need to further investigate HEBCS in other models of NAFLD as a lead to future use in clinical studies.

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model.

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.

Coating beef tallow with calcium soap improves dietary pellet quality and promotes an effective diet-induced obese mouse model

The obesity model is predominantly formed by feeding animals that are prone to obesity with high-fat diets, but this dietary intervention is not standardized. It is very difficult to pellet most high-fat diets, as they become rapidly oxidized due to their high-fat content. This study aimed to use calcium soap (Ca-soap) of beef tallow as a source of fat in high-fat mouse diets and to investigate its effects on pellet quality and its effectiveness in an obesity model. In the experiment, three diets were formed: a control diet (CD), a high-fat diet with beef tallow (HFD), and a high-fat diet containing beef tallow and Ca-soap of beef tallow (Ca-HFD). A total of 36 male C57BL/6 J mice aged six weeks were randomly divided into 3 groups: the Control (C), High-Fat (HF), and High-Fat with Ca-soap (Ca-HF) groups. The experiment lasted 20 weeks. Ca-HFD and HFD had higher hardness and pellet durability index (PDI) values than CD. Ca-HFD had a lower peroxide value than that of the HFD. At the end of the study, average body weight, body weight gain, food consumption, and calorie consumption were found to be the highest in the HF group and the lowest in the C group. The highest epididymal white adipose tissue (eWAT) ratio of the mice was seen in the Ca-HF group. Plasma triglyceride and insulin values ​​were higher in the HF group than in the C group. The highest level of steatosis was observed in the HF group. High body weight gain, fat deposition, hypercholesterolemia, hyperglycemia, glucose tolerance, and hepatic steatosis were observed in C57BL/6 J male mice fed the high-fat diets, but only HFD caused hyperinsulinemia. HFD and Ca-HFD can be used to model obesity, but only HFD can be used in type 2 diabetes modeling.

Sulforaphane Balances Ca2+ Homeostasis Injured by Excessive Fat via Mitochondria-Associated Membrane (MAM).

Mitochondria-associated membrane (MAM) connects endoplasmic reticulum (ER) and mitochondria plays a significant role in lipid metabolism and Ca2+ homeostasis. Albeit sulforaphane (SFN) shows potential in ameliorating excessive fat accumulation and mitochondrial function; whether MAM is a target of SFN and its underlying mechanisms are still unclear. High-fat-intake models are established both in vivo and in vitro. SFN widens the distance between ER and mitochondria and down-regulates MAM tether protein mitofusin-2. SFN reverses the increase of Ca2+ induced by fatty acid and inhibits the Ca2+ channel inositol-1,4,5-trisphosphate receptor (IP3R). Compared with high fat group, SFN alleviates Ca2+ overload in the mitochondria and suppresses mitochondrial calcium uniporter (MCU). Furthermore, SFN increases mitochondrial DNA quantities and mitochondria membrane potential, while decreasing reactive oxygen species (ROS) production. Finally, SFN increases mitochondria complexes IV content and ATP synthesis. These results suggest that SFN balances the Ca2+ homeostasis in the MAM through regulating Ca2+ flux by Ca2+ channel IP3R and MCU.

Amaranth Supplementation Improves Hepatic Lipid Dysmetabolism and Modulates Gut Microbiota in Mice Fed a High-Fat Diet.

Diet-induced obesity is often associated with gut microbiota dysbiosis, lipid metabolism disorders, and chronic inflammation. Consumption of the pseudocereal Amaranthus mangostanus has multiple nutritional benefits. We investigated the effects of dietary amaranth on lipid metabolism and gut microbiota in high-fat (HF) diet-fed mice. C57BL/6J mice were provided either a control diet, HF diet, or HF diet containing 10% amaranth powder (Ama) for 8 weeks. Ama supplementation significantly reduced the levels of triglycerides, total cholesterol, and phospholipids in the liver. Moreover, Ama supplementation downregulated the expression of lipogenesis-related genes including Hmgcr, Fdt1, and Sgle in the liver. The gut microbiota analysis showed that Ama supplementation reversed HF diet-induced reduction in bacterial diversity and richness. Additionally, beta diversity analysis of the inter-group variability in community structure showed a clear separation between the HF and Ama groups. Linear discriminant analysis effect size analysis revealed that 11 taxa were enriched in the Ama group, whereas 9 taxa were increased in the HF group. We found that family Porphyromonadaceae and unclassified S24-7 showed a strong positive and negative correlation with the lipid parameters, respectively. Taken together, these results indicated that dietary Ama may attenuate HF diet-induced deterioration of gut microbiota structure and hepatic lipid metabolism.

Metabolic Effects of pH Enhanced Ground Beef in Diet-induced Obese Mice

ObjectivesWestern diets, characterized by higher amounts of saturated fats, fatty proteins, and lower consumption of fruits, vegetables and lean proteins (alkaline diet) has been suggested to contribute to metabolic diseases (e.g., obesity), through low-grade metabolic acidosis (low pH). Hence, our objective was to test the effects of diets rich in beef prepared at various pH levels, in diet induced obese B6 mice. We hypothesized that metabolic health will be improved by consuming a diet containing pH-enhanced cooked ground beef, compared to a non pH-enhanced beef diet. MethodsB6 male and female mice were randomized (n = 5) into 6 groups; low fat (LF), pH-enhanced (ammonia) LF (LFN), high fat (HF), pH-enhanced HF (HFN), HF with beef (HFB), pH-enhanced HF beef (HFBN). Weight gain and food intake were measured weekly (for 12 weeks) and a glucose tolerance test (GTT) was performed at week 10. Tissues, including white adipose tissue (WAT) and liver were collected and used for histology, RNA and protein isolation, followed by analyses of gene (qRT-PCR) and proteins (Western blotting) related to fat and glucose metabolism. ResultsFinal body weight was significantly higher in HF group compared to LF and LFN groups in males, but not in females. Moreover, glucose clearance was significantly better in LF groups compared to HF group for both male and females. Interestingly, pH enhanced groups (HFN and HFBN) demonstrated significantly improved glucose clearance at the end of GTT compared to HF group only in males. Male WAT had smaller fat cell size, and greater fat cell number (P < 0.05) in HFN and HFBN compared to HF and HFB respectively. HFBN showed less hepatic fat accumulation in male mice compared to HFB group. Corroborating these, mRNA level of fatty acid oxidation marker Cpt1α was upregulated in HFBN group compared to HFB (P value 0.07) in male liver. ConclusionsFindings from this HF diet-induced obesity research suggest that there are potential metabolic benefits of increased dietary pH, through improved glucose clearance and fat metabolism. However, additional research is warranted to determine the underlying mechanisms and whether similar effects will be observed with LF pH-enhanced beef diets. These results can be further translated to human subjects to understand interactions between beef, pH and fat content on metabolic diseases. Funding SourcesEmpirical Foods, Inc.

Investigation of genetic markers for intramuscular fat in the hybrid Wagyu cattle with bulked segregant analysis

ulked Segregant Analysis (BSA) is a rapid strategy for identifying genetic markers in specific regions of the phenotypical population and it has been widely used for QTLs mapping in smaller mixed F2 and F3 populations. We applied a modified BSA method to assessed genome-wide homozygous and heterozygous linkage patterns in the Chinese Wagyu Beef Cattle F2/F3 mixed population. Two overlapped regions from F2 and F3 populations on autosomes were found with high-density heterozygote alleles between high and low intramuscular fat groups. Regions from 24.8 M ~ 29.6 M of chromosome 23 were identified as most significantly correlated to the intramuscular fat in our samples. We also identified other 4 potential loci on chromosomes 5, 9, 15, and 21 correlated with Intramuscular fat. This study provided a novel low-cost method for QTLs mapping and identify molecular markers of phenotypical changes in a small mixed population.

1183-P: Effect of Dairy Consumption and Its Fat Content on Gut Microbiota in Patients with Type 2 Diabetes: A Secondary Analysis of a Randomized Controlled Trial

Studies have demonstrated differences in gut microbial characteristics in diseases compared to healthy states. Knowledge of how diet alters the gut microbiome is limited by the lack of dietary interventional studies reporting on gut microbial characterization. We explored whether dairy foods differing in fat content alter the gut microbiota of patients with type 2 diabetes (T2D). We randomized 111 subjects with T2D into 3 groups: high-fat (HF) and low-fat (LF) dairy groups (≥ 3 servings/d of HF and LF dairy, respectively), and a control group (CON) maintained baseline dairy intake. Subjects were evaluated at baseline, 12 wk, and 24 wk. Next generation sequencing was performed using an Illumina NextSeq (2x150 bp, high output mode) in 32 subjects (16 in HF, 5 in LF, and 11 in CON). At 24 wk, featurewise testing revealed a higher Faecalibacterium prausnitzii abundance (MaAsLin2 coefficient = 0.0746, FDR-adjusted p = 0.0034; MaAsLin2 coefficient = 0.0691, FDR-adjusted p = 0.0195; respectively) and a higher Bifidobacterium pseudocatenulatum abundance (MaAsLin2 coefficient = 0.0022, FDR-adjusted p = 0.0673; MaAsLin2 coefficient = 0.0022, FDR-adjusted p = 0.1135; respectively) in LF compared to HF and CON in univariable models. Functional analyses revealed 11 significant associations including a lower abundance of UDP-glucose-derived O-antigen building blocks biosynthesis pathway (MaAsLin2 coefficient = –0.0006, FDR-adjusted p = 0.1584) related to lipopolysaccharides (LPS) production in HF compared to CON in a multivariable model and a lower L-methionine biosynthesis III pathway abundance (MaAsLin2 coefficient = –0.0015, FDR-adjusted p = 0.1975) in LF compared to HF in a univariable model. In conclusion, consumption of ≥ 3 servings/d of LF and HF dairy changed the gut microbiota of patients with T2D compared to CON. Further analysis will reveal whether a decrease in LPS biosynthesis-related pathway in HF influences inflammation. Disclosure S. Tomah: Stock/Shareholder; Self; Amarin Corporation plc. O. Hamdy: Advisory Panel; Self; Nestlé, Consultant; Self; Abbott, AstraZeneca, Sanofi, Research Support; Self; Eli Lilly and Company, Gilead Sciences, Inc., National Dairy Council, Novo Nordisk, Stock/Shareholder; Self; Healthimation, LLC. A. Kostic: Other Relationship; Self; DeepBiome Therapeutics, Inc., FitBiomics, Inc. J. Mitri: Consultant; Self; L-Nutra. J. E. Wilkinson: None. C. Li: None. M. Tasabehji: None. A. H. Eldib: None. M. Al-badri: None. H. Gardner: None. Funding National Dairy Council; National Institute of Diabetes and Digestive and Kidney Diseases

Effect of fat levels in early phase on growth performance and meat characteristics in twin lambs

This experiment aims to study the effects of dietary fat level during the suckling period on growth performance and meat characteristics in twin lambs. Thirty pairs of male twin Hu lambs were divided into two groups, namely high fat (HF) and normal fat (NF). Lambs in the HF group were fed milk replacer and starter containing 26.89% and 5.07% of fat, whereas those in the NF group were fed milk replacer and starter containing 15.15% and 2.80% of fat, respectively, from eight to 60 days of age. From 60 to 120 days of age, all lambs were fed a starter feed containing 2.80% fat. The results showed that lambs fed HF diet had higher body weight (12.78 kg versus 11.63 kg, P = 0.020), average daily gain (162.4 g/day versus 141.1 g/day, P = 0.019), apparent digestibility of organic matter (P = 0.018) and gross energy (P &amp;lt; 0.001). No difference was observed between HF and NF group in slaughter performance during eight to 60 days of age. Lambs fed HF diet had higher body weight at 120 days of age (P = 0.035). However, no difference was observed in nutrient digestibility, slaughter performance or meat quality at 120 days of age. In summary, the HF diet in the suckling period showed long-lasting beneficial effects on the growth performance of lambs.

Protective effect of baicalein on high fat-induced hepatocytes oxidative damage

Objective: To investigate the effect of baicalein in improving non-alcoholic fatty liver disease caused by high fat-induced oxidative damage in mice. Methods: Male C57BL/6J mice weighing 18-20 g were randomly divided into 4 groups: normal control group (C, 10% fat for energy), high-fat group (H, 60% fat for energy), high-fat + scutellaria baicalein group (H+B, baicalein: 400 mg·kg(-1)·bw(-1)), and baicalein control group (B, baicalein: 400 mg·kg(-1)·bw(-1)). After 12 weeks, mice were sacrificed, and the tissue samples were collected. Liver pathological changes were observed by hematoxylin and eosin staining. Mitochondrial morphology was examined by ultramicropathology. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and mitochondrial membrane potential (MMP) changing levels in the liver were determined by kit. Sestrin2 and protein carbonylation (PCOS) levels were detected by Western blotting. Small interfering RNA (siRNA) was used to knock-down the Sestrin2 protein expression in HepG2 cells. Intramyocellular lipid changes in HepG2 cells was detected by fluorescent dye BODIPY493/503. One way ANOVA was used LSD pairwise comparison method was used to test the statistical difference. Results: Compared with the normal control group, high-fat fed caused significant fatty degeneration, decreased GSH and SOD levels (P ​​< 0.05), increased MDA and protein carbonylation levels, and increased Sestrin2 expression (P < 0.05) in mice. Mitochondrial shape changes, swelling, lack of cristae, and MMP was down-regulated by 33.3% (t = 13.456, P ​​< 0.001). Baicalein intervention had effectively inhibited hepatic steatosis and oxidative damage caused by high-fat fed, and further up-regulated Sestrin2 expression, MMP (t = 10.104, P ​​< 0.001), and significantly alleviated liver damage in mice. Sestrin2 expression knock-down had further increased the intracellular lipid deposition and PCOs expression (P ​​< 0.05), and reduced baicalein ability to antagonize lipid deposition and antioxidant capacity in Hep2 cells. Conclusion: Baicalein alleviate non-alcoholic fatty liver by regulating Sestrin2 expression and high-fat fed-induced liver oxidative damage.

The relationship between dietary fat intake, impulsive choice, and metabolic health

Unhealthful foods are convenient, ubiquitous, and inexpensive. Overconsumption of unhealthful foods can result in disease states such as obesity and Type 2 diabetes. In addition to the physiological consequences of unhealthful foods, research in rats has shown that diets high in processed fat and sugar induce impulsive choice behavior. Research in humans has demonstrated a link between metabolic health and impulsive choice, but most investigations have not included diet. We investigated how dietary fat intake interacts with body fat percentage, fasting glucose, insulin response, and systemic inflammation levels to predict impulsive choices in humans. Participants were split into either Control (<35% calories from fat) or High-Fat (≥40% calories from fat) groups based on self-reported dietary intake, completed an impulsive choice task, and underwent testing to determine their body fat, glucose, insulin response, and inflammation levels. High-fat diets were not predictive of impulsive choices, but added sugar was predictive. Body fat percentage was associated with impulsive choices only in the group who reported consuming high-fat diets. In addition, fasting glucose was associated with impulsive choices in the control group. Therefore, metabolic health and dietary fat intake interacted to predict impulsive choices. These findings indicate that knowledge of dietary patterns coupled with metabolic health markers may help us better understand impulsive choices, thereby improving our ability to target individuals who could benefit from interventions to reduce impulsive choice behavior, with the goal of promoting more self-controlled food choices.

Effects of consumption of acerola, cashew and guava by-products on adiposity and redox homeostasis of adipose tissue in obese rats

Fruit by-products contain phytochemicals, fibers and other components that can improve the redox imbalance of obesity. The objective was to evaluate the effects of consumption of by-products of acerola, cashew and guava on the adiposity and redox homeostasis of adipose tissue in obese rats. The animals were separated into 5 groups, control (CTL), high fat (HF), HF supplemented with acerola (HFA), cashew (HFC) and guava (HFG). Thiol quantification, lipid profile, catalase (CAT) and glutathione peroxidase (GPX) test were performed. TGL and VLDL levels were increased in HF group, and the treated groups did not change the lipid profile. CAT activity was increased in HFA and HFG groups. HFA was able to reduce the weight of the subcutaneous cushion. Treatment with fruit by-products did not alter weight gain, energy efficiency and body weight. Thus, the by-products of acerola and guava can be used as a sustainable alternative in the treatment of obesity.

Effect of fermented bee pollen on metabolic syndrome in high-fat diet-induced mice

Bee pollen has potential in preventing metabolic syndrome (MetS). The present study aimed to investigate the effect of yeast-fermented wall-broken bee pollen (YB) intervention on ICR mice with MetS induced with a high-fat (HF) diet. After YB intervention in mice for 16 weeks, the effect on alleviating MetS was evaluated based on MetS serum parameters, hepatic oxidant status markers and gut microbial populations. The results of animal experiment showed that YB intervention attenuated MetS. Based on multivariate statistical analysis results, YB treatment significantly increased glutathione S-transferase (GST) and catalase (CAT) activities and decreased the malondialdehyde (MDA) level in the liver. Further investigation showed that YB restored the Nrf-2-Keap-1 pathway to alleviate oxidative stress. Additionally, gut microbial community analysis revealed that YB restored the increase in the Firmicutes to Bacteroidetes (F/B) ratio (6.94 for the HF group and 3.74 for HF+YB group) and improved Lactobacillus and Lactococcus abundance induced by the HF diet. Overall, YB improved function and prevented MetS by modulating the gut microbiota and alleviating oxidative stress.

Micro-PIXE with 3.5 MeV protons for the study of low copper concentrations in atherosclerotic artery

The onset and progression of many degenerative diseases including atherosclerosis, have been shown to directly link to the presence/absence of certain metal ions. Consequently, the detection of these ions in tissues may improve the understanding of the driving pathophysiology. The Cu content during atherosclerosis development has not been studied due to its low concentration involved. In this work, the Cu level in atherosclerotic rabbit tissue is determined using PIXE with a 3.5 MeV proton beam. The arteries of three animal groups fed with different diets were studied: group 1, rabbits on normal standard diet, group 2, on High Fat Diet (HFD) and group 3, on HFD + Zinc diet. Zinc supplement has been proven to inhibit the beginning of atherosclerotic lesion. The result of this study shows that the Cu levels in all the atherosclerotic lesions were lower than that in the arterial walls of the samples in HFD group.

Voltage-gated potassium channels are involved in oxymatrine-regulated islet function in rat islet β cells and INS-1 cells.

Objective(s):Oxymatrine can regulate glucose metabolism. But the underlying mechanisms remain unclear. We investigated the relationship of oxymatrine and voltage-gated potassium (Kv) channel in rat islet β cells and INS-1 cells.Materials and Methods:Insulin secretion and Kv channel currents were tested by radioimmunoassay and patch-clamp technique, respectively. The INS-1 cell viability was detected using cell counting kit-8 experiments. Flowcytometry analysis and western blot were employed for cell apoptosis and protein levels, respectively. INS-1 cell proliferation was assessed by the 5-Ethynyl-2’- deoxyuridine method. Results:Oxymatrine potentiated insulin secretion at high glucose (P<0.01 vs 11.1 G, P<0.01 vs 16.7 G) and inhibited KV currents at 40 mV (45.73±15.34 pA/pF for oxymatrine, 73.80±19.23 pA/pF for control, P<0.05). After the INS-1 cells were treated with oxymatrine for 12 and 24 hr, KV2.1 channel protein was up-regulated (P<0.01 vs Control). At the same time, compared with the high glucose and high fat group, cell viability and proliferation ability were increased (P<0.01). The cell apoptotic rate was reduced, reaching 17.30%±1.00% at 12 hr and 10.35%±1.52% at 24 hr (P<0.01). These protective effects of oxymatrine were reversed by using Stromatoxin-1, a kv channel inhibitor.Conclusion:The results indicate that oxymatrine can stimulate insulin secretion and decrease kv channel currents in islet β cells. Besides, oxymatrine also increases cell viability, proliferation, and reduces cell apoptosis in INS-1 cells. The effects of oxymatrine are related to kv channels. This finding provides new insight into the mechanisms of oxymatrine-regulated islet function.

The therapeutic effects of berberine plus sitagliptin in a rat model of fatty liver disease.

Objective(s):Fatty liver disease (FLD) is a disorder related to accumulation of excess fat within the hepatocytes. In this study, the effects of Berberine, a natural compound, and Sitagliptin as a DPP-4 inhibitor, were observed in a rat model of FLD.Materials and Methods:Forty male rats were divided into five groups (n=6) including the control group (normal food and water), high-fat group (high-fat diet (HF) for 6 weeks), Berberine group (HF with oral administration of Berberine at 150 mg/kg for 6 weeks), Sitagliptin group (HF with oral administration of Sitagliptin at 10 mg/kg for 6 weeks), and Berberine/ Sitagliptin group (HF diet within combination with oral administration of Berberine 75 mg/kg and Sitagliptin 5 mg/kg for 6 weeks). Animals were examined for weight gain, serum and hepatic biochemical parameters, tissue histology, expression of glucose transporter type 4 (GLUT4) mRNA, and protein expression of Adiponectin receptor2 (AdipoR2) and extracellular signal-regulated kinase (ERK) and phoERK.Results:The results showed that ALT, AST, lipid profile, insulin, glucose, MDA, and TNF-α were significantly improved in high-fat rats treated with Berberine/ Sitagliptin compared with HF and Sitagliptin, and Berberine alone groups. SOD and adiponectin levels in Berberine/ Sitagliptin group were also significantly increased compared with the other groups. Immunoblot analysis showed that the expression of pho-ERK/ERK was significantly decreased and expression of AdipoR2 significantly increased in the Berberine/ Sitagliptin group compared with other groups.Conclusion:Co-administration of Berberine and Sitagliptin is an effective therapeutic regimen for conditions associated with hyperlipidemia.

Plasma Free Fatty Acids and Metabolic Effect in Type 2 Diabetes, an Ancillary Study from a Randomized Clinical Trial.

Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias. Pentadecanoic acid, heptadecanoic acid and trans-palmitoleic acid are fatty acids that are not synthesized endogenously but are obtained from the diet, particularly dairy, making them reasonable biomarkers of dairy consumption. We investigated the association of dairy fatty acid biomarkers with glycated hemoglobin (HbA1c) and cardiovascular risk factors in type 2 diabetes (T2D). In a clinical trial, 111 participants with T2D (age 58.5 ± 8.9 years, HbA1c 8.09 ± 0.96%) were randomized into three groups: a control group that maintained baseline dairy intake, a low-fat (LF) group that incorporated ≥3 servings/day of LF dairy and a high-fat (HF) group that incorporated ≥3 servings/day of HF dairy. We compared the fatty acids (FA) composition between the three groups at 24 weeks. Pentadecanoic acid and trans-palmitoleic acid increased in the HF group by 14.1% ± 5.4% and 17.5% ± 5.1%, respectively, but not in the control and LF groups (p = 0.0474 and p = 0.0025 for group-by-time interaction, respectively). Those increases were positively associated with changes in total cholesterol, very-low-density lipoprotein cholesterol VLDL-C and triglycerides but were not associated with changes in HbA1c from baseline to 24 weeks. These results suggest that the intervention was successful and that participants were likely compliant, which supports the validity of the main trial.

The Effects of Exercise and Restriction of Sugar-Sweetened Beverages on Muscle Function and Autophagy Regulation in High-Fat High-Sucrose-Fed Obesity Mice.

BackgroundAutophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training.MethodsObese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively.ResultsSR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group.ConclusionSR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.