scholarly journals Co-Administration of Conjugated Linoleic Acid and Rosiglitazone Increases Atherogenic Co-Efficient and Alters Isoprenaline-Induced Vasodilatation in Rats Fed High Fat Diet

2018 ◽  
pp. 729-740
Author(s):  
B. K. CHAI ◽  
Y. S. LAU ◽  
B. J. LOONG ◽  
M. M. RAIS ◽  
K. N. TING ◽  
...  

The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (Rmax=53±4.7 %; pEC50=6±0.2) compared to endothelium-intact aortas (Rmax=100±9.9 %; pEC50=7±0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.

2021 ◽  
Vol 35 (4) ◽  
Author(s):  
Haoyu Li ◽  
Pan Zhuang ◽  
Yu Zhang ◽  
Qiyang Shou ◽  
Yanhua Lu ◽  
...  

2008 ◽  
Vol 294 (5) ◽  
pp. E833-E840 ◽  
Author(s):  
Masaki Tsunoda ◽  
Naoki Kobayashi ◽  
Tomohiro Ide ◽  
Mari Utsumi ◽  
Michiaki Nagasawa ◽  
...  

Agonism of peroxisome proliferator-activated receptor (PPAR) α, a key regulator of lipid metabolism, leads to amelioration of lipid abnormalities in dyslipidemic patients. However, whether PPARα agonism is an effective form of therapy for obesity-related insulin resistance associated with lipid abnormalities is unclear. The present study investigated the effects of a potent and subtype-selective PPARα agonist, KRP-101, in a nonrodent insulin-resistant animal model under pair-fed conditions. Beagle dogs were fed a high-fat diet for 24 wk to induce insulin resistance. During the final 12 wk, 0.03 mg·kg−1·day−1 KRP-101 ( n = 5) or vehicle ( n = 5) was administered orally once a day. KRP-101 administration resulted in a significantly lower weight of overall visceral fat, which is associated with increased adiponectin and decreased leptin in serum. KRP-101 administration improved hyperglycemia and hyperinsulinemia as well as dyslipidemia in dogs fed a high-fat diet. Oral glucose tolerance test showed that KRP-101 administration improved glucose intolerance. The KRP-101 group showed a markedly lower hepatic triglyceride concentration. Lipid oxidation was increased in the liver and skeletal muscles of the KRP-101 group. These findings in the dog model suggest that the use of potent and subtype-selective PPARα agonists as a potentially relevant therapeutic approach to treat human insulin resistance associated with visceral obesity.


2018 ◽  
Vol 126 (06) ◽  
pp. 379-386 ◽  
Author(s):  
Priscila Bezan ◽  
Héric Holland ◽  
Gabriela de Castro ◽  
João Cardoso ◽  
Paula Ovidio ◽  
...  

AbstractObesity and related diseases are becoming more prevalent. Conjugated linoleic acid (CLA) might be a useful coadjutant treatment helping to decrease fat mass. However, the precise impact of CLA is unclear because the decreased body fat mass is followed by an increase in insulin resistance. This study aimed to evaluate some of the consequences of a high dose of CLA in rats fed a normal low fat or a high fat diet for 30 days. Male Wistar rats were separated into 4 groups (each n = 10): Control group receiving 7% fat (soybean oil); CLA group receiving 4% soybean oil and 3% CLA mixture; animal fat (AF) group, receiving 45% fat (lard); and animal fat plus CLA (AF+CLA) group, receiving 42% lard and 3% CLA mixture. The CLA mixture contained 39.32 mole% c9,t11-CLA and 40.50 mole% t10,c12-CLA. After 30 days, both CLA groups (CLA and AF+CLA groups) developed insulin resistance, with an increase in glucose in the fasting state and in an insulin tolerance test. The CLA group had increased liver weight and percentage of saturated fatty acids in liver and adipose tissue. Feeding the high fat diet resulted in increased hepatic triacylglycerol accumulation and this was exacerbated by dietary CLA. It is concluded that a high dose of CLA mixture increases insulin resistance and exacerbates hepatic steatosis when combined with a high fat diet.


2020 ◽  
Vol 11 (8) ◽  
pp. 753-766
Author(s):  
A.I. Zaydi ◽  
L.-C. Lew ◽  
Y.-Y. Hor ◽  
M.H. Jaafar ◽  
L.-O. Chuah ◽  
...  

Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (109 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats (P<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Michael J Duryee ◽  
Anand Dusad ◽  
Scott W Shurmur ◽  
Michael D Johnston ◽  
Robert P Garvin ◽  
...  

Introduction Malondialdehyde/Acetaldehyde (MAA) modified proteins have been suggested to play a role in the development/progression of atherosclerosis. Circulating antibodies directed against these proteins have recently been shown to be associated with the severity of the disease. More specifically, the isotype of the antibody to MAA correlated with either an acute MI (IgG) or stable plaque formation (IgA) formation. MAA is thought to form as a result of the oxidation of fat(s) and thus the concentration and antibody response should reflect the amount of fat in the diet. Objective The purpose of this study was to evaluate the antibody responses to MAA modified proteins following immunization and high fat western diet feeding in rats. Methods Male Sprague Dawley rats were immunized with MAA-modified protein weekly for 5 weeks and then assayed for antibodies to these proteins. Animals were then separated into the following groups: chow sham, chow MAA immunized, high fat sham, and high fat MAA immunized. The high fat animals were fed a Western diet with 2-thiouracil for 12 weeks, bled every 3 weeks, and serum assayed for the presence of circulating MAA antibodies. Results Prior to feeding with high fat diet, rats immunized with MAA-modified protein had a significant increase (P<0.001) in serum antibodies directed against these modified proteins compared to controls (N of 4 per group). Following feeding of high fat diet antibody concentrations increased 6 fold in the high fat MAA immunized group compared to the chow MAA immunized group (P<0.05). Antibodies in the high fat sham and chow sham had only minimal increases in antibodies to these proteins. Conclusions These data demonstrate that following immunization with MAA-modified proteins, circulating antibodies are produced that increase following consumption of a high fat Western diet. It suggests that MAA-modified proteins are produced at low levels following normal diet, producing antibodies which act as a normal clearance method for altered protein. When high fat consumption increases these antibody levels are increased in response to the oxidative stress. Implications Use of these antibodies as a biomarker in the future may help predict the onset or progression of atherosclerosis.


2018 ◽  
Vol 237 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Keerati Wanchai ◽  
Sakawdaurn Yasom ◽  
Wannipa Tunapong ◽  
Titikorn Chunchai ◽  
Parameth Thiennimitr ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1699-1699
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon

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.


Sign in / Sign up

Export Citation Format

Share Document