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Prashanth A.,National Institute of Nutrition ICMR | Jeyakumar S.M.,National Institute of Nutrition ICMR | Giridharan N.V.,National Center for Laboratory Animal science | Vajreswari A.,National Institute of Nutrition ICMR
Journal of Atherosclerosis and Thrombosis | Year: 2014

Aim: Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.Methods: Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.Results: Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyl-transferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.Conclusions: Chronic feeding of a vitamin A-enriched diet in hypercholesterolemic obese rats normalizes the plasma HDL-C level and presumably improves RCT, with an effective dose of 52 mg/kg diet. Further studies should focus on the pharmacological potential of vitamin A supplementation to correct an abnormal human obesity-associated lipoprotein metabolism. © 2014, Japan Atherosclerosis Society. All rights reserved. Source


Sinha J.K.,National Institute of Nutrition NIN | Ghosh S.,National Institute of Nutrition NIN | Swain U.,Jawaharlal Nehru Technological University | Giridharan N.V.,National Center for Laboratory Animal science | Raghunath M.,National Institute of Nutrition NIN
Neuroscience | Year: 2014

Wistar of the National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all traits of metabolic syndrome and has a remarkably reduced lifespan (1.5. years as compared to 3. years in parental WNIN rats), albeit, the factors associated with premature aging are not well understood. Considering that oxidative stress and DNA damage are crucial players associated with senescence, we analyzed oxidative stress markers like lipid peroxidation and protein oxidation; DNA damage in terms of both single-stranded and double-stranded breaks and the activity of antioxidant enzymes: superoxide dismutase and catalase in brain regions of these animals. Our study revealed that the magnitude of oxidative stress and DNA damage in the neocortex and hippocampus of 3-month-old WNIN/Ob obese rats is as high as that seen in 15-month-old parental WNIN control rats. Concurrently, the antioxidant enzyme activity was significantly decreased. From these results, it can be concluded that increased oxidative stress-induced damage of macromolecules, probably due to reduced activity of antioxidant enzymes, is associated with premature aging in WNIN/Ob obese rats. © 2014 IBRO. Source


Singh H.,National Institute of Nutrition ICMR | Giridharan N.,National Center for Laboratory Animal science | Bhonde R.R.,Manipal University India | Venkatesan V.,National Institute of Nutrition ICMR
Islets | Year: 2013

Development of appropriate animal model systems have greatly helped our understanding of the basic mechanism(s) of several degenerative diseases. WNIN/GR-Ob - a mutant rat strain developed at the National Center for Laboratory Animal Sciences facility of National Institute of Nutrition, is a new animal model ideal to study the metabolic syndrome since it is obese with impaired glucose tolerance and also exhibits several secondary complications. The present study was performed in the pancreas of this mutant model to assess the global gene expression (microarray) to assess the transcriptome level changes in situ depicting inflammation, obesity, IR and diabetes in these animals. Our findings suggest an interplay of several confounding factors in pancreas which include inflammation/macrophage infiltration/apoptosis/oxidative and endoplasmic reticulum stress, all contributing for the shift toward pro-inflammation. We were able to phenotypically correlate the metabolic alterations vis-a-vis candidate genes (array analyses) compared between mutants and its age matched, parental controls. We advocate that the data reported here would provide a suitable insight in to the pathophysiology of metabolic syndrome. © 2013 Landes Bioscience. Source


Prashanth A.,National Institute of Nutrition ICMR | Jeyakumar S.M.,National Institute of Nutrition ICMR | Singotamu L.,National Institute of Nutrition ICMR | Harishankar N.,National Center for Laboratory Animal science | And 2 more authors.
Nutrition and Metabolism | Year: 2014

Background: Previously, we reported that vitamin A-enriched diet (129 mg/kg diet) intake reduces the adiposity development in obese rats of WNIN/Ob strain. Here, we hypothesize that dose lesser than 129 mg of vitamin A/kg diet would also be effective in ameliorating the development of obesity in these rats.Methods. Five-month-old male lean and obese rats designated as A & B were divided into four subgroups (I, II, III and IV) consisting of 8 rats from each phenotype and received diets containing 2.6 mg (control group), 26 mg, 52 mg and 129 mg vitamin A/kg diet as retinyl palmitate for 20 weeks. Body composition and morphological analysis of brown adipose tissue (BAT) was analyzed. Expression of uncoupling protein 1 (UCP1), retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) in BAT and levels of Bcl2 and Bax in epididymal white adipose tissue (eWAT) were determined by immunoblotting.Results: Vitamin A supplementation to obese rats at doses of 52 and 129 mg/kg diet showed reduced body weight gain and adiposity compared to control diet-fed obese rats receiving 2.6 mg of vitamin A/kg diet. In BAT of obese rats, vitamin A supplementation at doses of 26 and 52 mg of vitamin A/kg diet resulted in increased UCP1 expression with concomitant decrease in RARα and RXRα levels compared to control diet-fed obese rats. Further, transmission electron microscopy study revealed an increase in number of BAT mitochondria of obese rats supplemented with 26 and 52 mg of vitamin A/kg diet. Also, obese rats fed on 52 mg/kg diet resulted in increased apoptosis by altering the ratio of Bcl2 to Bax protein levels in eWAT. Notably, most of these changes were not observed in lean rats fed vitamin A-enriched diets.Conclusion: In conclusion, chronic consumption of 52 mg of vitamin A/kg diet seems to be an effective dose in ameliorating obesity possibly through mitochondriogenesis, UCP1-mediated thermogenesis in BAT and apoptosis in eWAT of obese rats. Therefore, the role of dietary vitamin A in correcting human obesity would be of unquestionable relevance and can only be addressed by future studies. © 2014Prashanth et al.; licensee BioMed Central Ltd. Source


Sasikala M.,Asian Institute of Gastroenterology | Rao G.V.,Asian Institute of Gastroenterology | Vijayalakshmi V.,National Institute of Nutrition | Pradeep R.,Asian Institute of Gastroenterology | And 9 more authors.
Transplantation | Year: 2013

BACKGROUND: Long-term survival and functions of encapsulated islet grafts need to be evaluated in the absence of immunosuppression. The present study aimed to assess the viability and functions of macroencapsulated islets grafted in nonhuman primates without immunosuppression for 1 year. METHODS: Islet transplantations were performed in partially pancreatectomized rhesus monkeys (two autologous and four allogenic) without immunosuppression using immunoisolatory devices. Macroencapsulated islets were implanted subcutaneously (5000-8000 IEQ/device) at two sites (left thigh and interscapular region) and were explanted at 2, 6, and 12 months after implantation. Staining for viability and apoptosis, in vivo and in vitro glucose-stimulated insulin release, expression of insulin and glucagon genes, and histopathologic examination of the device were used to assess engraftment potential, viability, and functions of islets. Animals were regularly monitored for dietary intake, body weight, and fasting blood glucose levels after islet transplantation. RESULTS: Devices explanted showed vascularization at the end of 2, 6, and 12 months with occasional lymphocytes and minimal fibrosis outside the device. Flow cytometric analysis revealed 97.9%±1.5% and 94.3%±5.71% viable β cells in interscapular site and thigh in autologous recipients and 85.6%±4.01% (interscapular site) and 74.1%±12.05% (thigh) viable β cells in allogenic islet recipients. In vivo glucose challenge test revealed significantly increased glucose-stimulated insulin release (P=0.028) in the left thigh with implant (17.58±3.13 mU/L) compared with the thigh without implant (9.86±1.063 mU/L). Insulin and glucagon gene expression was evident in islets recovered from explanted device. CONCLUSIONS: These results indicate that subcutaneous implantation of macroencapsulated islets is minimally invasive and has potential for transplantation without immunosuppression. Copyright © 2013 by Lippincott Williams & Wilkins. Source

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