Abstract # P-20: 11b-Hydroxysteroid Dehydrogenase 1 Regulation in High Fat Diet Induced Insulin Resistant Rats and Rats Treated with Sutherlandia Frutescens

2016 ◽  
Vol 22 ◽  
pp. 23
Author(s):  
Ngozi F. Nnolum-Orji ◽  
Saartjie Roux ◽  
Janine Mackenzie ◽  
Disang Lekutlane
Keyword(s):  
High Fat Diet ◽  
Hydroxysteroid Dehydrogenase ◽  
High Fat ◽  
Insulin Resistant ◽  
Sutherlandia Frutescens

Hyperbaric oxygen therapy attenuates D-galactose-induced-age-related cardiac dysfunction through mitigating cardiac mitochondrial dysfunction in pre-diabetic rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bo-Htay ◽  
T Shwe ◽  
S Palee ◽  
T Pattarasakulchai ◽  
K Shinlapawittayatorn ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Normal Diet ◽  
Lv Function ◽  
High Fat ◽  
Insulin Resistant ◽  
Lv Dysfunction ◽  
Age Related ◽  
Mitochondrial Functions

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants

scholarly journals IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

2015 ◽  
Vol 309 (8) ◽  
pp. R835-R844 ◽  
Author(s):  
Emanuele Loro ◽  
Erin L. Seifert ◽  
Cynthia Moffat ◽  
Freddy Romero ◽  
Manoj K. Mishra ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Wide Distribution ◽  
Liver Fat ◽  
Acid Oxidation ◽  
Direct Effects ◽  
High Fat ◽  
Binding Partner ◽  
Insulin Resistant ◽  
Diet Induced Obesity

IL-15Rα is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15Rα take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15Rα promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15Rα on metabolism and obesity are currently unknown. We report that mice lacking IL-15Rα (IL-15Rα−/−) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Rα−/− mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15Rα−/− are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Rα in metabolism and obesity.

scholarly journals Fiber type-specific effects of acute exercise on insulin-stimulated AS160 phosphorylation in insulin-resistant rat skeletal muscle

2019 ◽  
Vol 317 (6) ◽  
pp. E984-E998
Author(s):  
Mark W. Pataky ◽  
Sydney L. Van Acker ◽  
Rhea Dhingra ◽  
Marina M. Freeburg ◽  
Edward B. Arias ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Acute Exercise ◽  
Fiber Type ◽  
Type I ◽  
Fiber Types ◽  
High Fat ◽  
Insulin Resistant ◽  
Specific Effects ◽  
Heterogeneous Tissue ◽  
Whole Muscle

Muscle is a heterogeneous tissue composed of multiple fiber types. Earlier research revealed fiber type-selective postexercise effects on insulin-stimulated glucose uptake (ISGU) from insulin-resistant rats (increased for type IIA, IIB, IIBX, and IIX, but not type I). In whole muscle from insulin-resistant rats, the exercise increase in ISGU is accompanied by an exercise increase in insulin-stimulated AS160 phosphorylation (pAS160), an ISGU-regulating protein. We hypothesized that, in insulin-resistant muscle, the fiber type-selective exercise effects on ISGU would correspond to the fiber type-selective exercise effects on pAS160. Rats were fed a 2-wk high-fat diet (HFD) and remained sedentary (SED) or exercised before epitrochlearis muscles were dissected either immediately postexercise (IPEX) or at 3 h postexercise (3hPEX) using an exercise protocol that previously revealed fiber type-selective effects on ISGU. 3hPEX muscles and SED controls were incubated ± 100µU/mL insulin. Individual myofibers were isolated and pooled on the basis of myosin heavy chain (MHC) expression, and key phosphoproteins were measured. Myofiber glycogen and MHC expression were evaluated in muscles from other SED, IPEX, and 3hPEX rats. Insulin-stimulated pAktSer473 and pAktThr308 were unaltered by exercise in all fiber types. Insulin-stimulated pAS160 was greater for 3hPEX vs. SED on at least one phosphosite (Ser588, Thr642, and/or Ser704) in type IIA, IIBX, and IIB fibers, but not in type I or IIX fibers. Both IPEX and 3hPEX glycogen were decreased versus SED in all fiber types. These results provided evidence that fiber type-specific pAS160 in insulin-resistant muscle may play a role in the previously reported fiber type-specific elevation in ISGU in some, but not all, fiber types.

scholarly journals CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice

2019 ◽  
Vol 317 (6) ◽  
pp. E973-E983 ◽  
Author(s):  
Annie Hasib ◽  
Chandani K. Hennayake ◽  
Deanna P. Bracy ◽  
Aimée R. Bugler-Lamb ◽  
Louise Lantier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
High Fat Diet ◽  
Critical Role ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.

Atorvastatin modulates the DDAH1/ADMA system in high-fat diet-induced insulin-resistant rats with endothelial dysfunction

2012 ◽  
Vol 17 (6) ◽  
pp. 416-423 ◽  
Author(s):  
Po Chen ◽  
Ke Xia ◽  
Zhenyu Zhao ◽  
Xu Deng ◽  
Tianlun Yang
Keyword(s):  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
High Fat ◽  
Insulin Resistant

scholarly journals Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats

2018 ◽  
Vol 237 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Keerati Wanchai ◽  
Sakawdaurn Yasom ◽  
Wannipa Tunapong ◽  
Titikorn Chunchai ◽  
Parameth Thiennimitr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Renal Function ◽  
High Fat Diet ◽  
Organic Anion ◽  
Normal Diet ◽  
Organic Anion Transporter ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects ◽  
Anion Transporter

Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 function. These alterations were improved by XOS supplementation. Renal MDA level and the expression of AT1R, NOX4, p67phox, 4-HNE, phosphorylated PKCα and ERK1/2 were significantly decreased after XOS treatment. In addition, Nrf2-Keap1 pathway, SOD2 and GCLC expression as well as renal apoptosis were also significantly reduced by XOS. These data suggest that XOS could indirectly restore renal function and Oat3 function via the reduction of oxidative stress and apoptosis through the modulating of AT1R-PKCα-NOXs activation in obese insulin-resistant rats. These attenuations were instigated by the improvement of obesity, hyperlipidemia and insulin resistance.

scholarly journals Herring Milt and Herring Milt Protein Hydrolysate Are Equally Effective in Improving Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese- and Insulin-Resistant Mice

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 635
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Cell Function ◽  
Protein Hydrolysate ◽  
High Fat ◽  
Β Cell ◽  
Insulin Resistant ◽  
Β Cell Function ◽  
Casein Protein ◽  
Dietary Casein

Although genetic predisposition influences the onset and progression of insulin resistance and diabetes, dietary nutrients are critical. In general, protein is beneficial relative to carbohydrate and fat but dependent on protein source. Our recent study demonstrated that 70% replacement of dietary casein protein with the equivalent quantity of protein derived from herring milt protein hydrolysate (HMPH; herring milt with proteins being enzymatically hydrolyzed) significantly improved insulin resistance and glucose homeostasis in high-fat diet-induced obese mice. As production of protein hydrolysate increases the cost of the product, it is important to determine whether a simply dried and ground herring milt product possesses similar benefits. Therefore, the current study was conducted to investigate the effect of herring milt dry powder (HMDP) on glucose control and the associated metabolic phenotypes and further to compare its efficacy with HMPH. Male C57BL/6J mice on a high-fat diet for 7 weeks were randomized based on body weight and blood glucose into three groups. One group continued on the high-fat diet and was used as the insulin-resistant/diabetic control and the other two groups were given the high-fat diet modified to have 70% of casein protein being replaced with the same amount of protein from HMDP or HMPH. A group of mice on a low-fat diet all the time was used as the normal control. The results demonstrated that mice on the high-fat diet increased weight gain and showed higher blood concentrations of glucose, insulin, and leptin, as well as impaired glucose tolerance and pancreatic β-cell function relative to those on the normal control diet. In comparison with the high-fat diet, the replacement of 70% dietary casein protein with the same amount of HMDP or HMPH protein decreased weight gain and significantly improved the aforementioned biomarkers, insulin sensitivity or resistance, and β-cell function. The HMDP and HMPH showed similar effects on every parameter except blood lipids where HMDP decreased total cholesterol and non-HDL-cholesterol levels while the effect of HMPH was not significant. The results demonstrate that substituting 70% of dietary casein protein with the equivalent amount of HMDP or HMPH protein protects against obesity and diabetes, and HMDP is also beneficial to cholesterol homeostasis.

scholarly journals Herring Milt and Herring Milt Protein Hydrolysate Reduce Weight Gain and Improve Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1699-1699
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Cell Function ◽  
Protein Hydrolysate ◽  
Oral Glucose ◽  
High Fat ◽  
Low Fat ◽  
Insulin Resistant ◽  
Low Fat Diet ◽  
Dietary Casein

Abstract Objectives The present study was designed to examine the effect of herring milt dry powder (HMDP) on glucose homeostasis and related metabolic phenotypes and compare its efficacy with herring milt protein hydrolysate (HMPH) in diet-induced obese and insulin resistant mice. Methods Male C57BL/6 J mice were pretreated with a high-fat diet for 7 weeks were divided into 3 groups where one group continued on the high-fat diet and used as the obese and insulin resistant control (HFC) and the other two groups were fed a modified HFC diet where 70% of casein was replaced with an equal percentage of protein derived from HMDP or HMPH. A group of mice fed a low-fat diet all the time was used as the normal or low-fat control (LFC). Body weight was obtained weekly and food intake was recorded daily. Semi-fating (4–6 hr) blood glucose was measured every other week using a glucometer using the blood from tail vein. Oral glucose tolerance was measured twice during weeks 5 and 9, respectively, and insulin tolerance was determined during week 7 of the treatment. At the end of the experiment, serum was obtained following overnight fasting for the measurement of fasting insulin, leptin, free fatty acids and lipids as well as other glucose metabolism-related biomarkers. Results During the 9-week treatment period, mice on the high-fat diet maintained significantly higher body weight and semi-fasting blood glucose levels and exhibited impaired oral glucose tolerance and insulin resistance relative to mice on the low-fat diet. At the end of the study, the analysis of fasting blood samples revealed that mice on the high-fat diet had increases in serum insulin, leptin, free fatty acids and cholesterol levels. Mice fed the high-fat diet also showed an increase in insulin resistance index and a decrease in β-cell function index. Compared to mice on the high-fat diet, the 70% replacement of dietary casein with an equal percentage of protein derived from HMDP or HMPH reversed or markedly improved these parameters, and HMDP and HMPH showed similar effects. Conclusions The results demonstrate that replacing dietary casein with the same amount of protein derived from either HMDP or HMPH prevents and improves high-fat-diet-induced obesity and insulin resistance. Funding Sources Atlantic Canada Opportunity Agency through the Atlantic Innovation Fund grant (no. 193,594) and National Research Council of Canada – NHP program.

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