Hyderabad andhra Pradesh, India
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Sakamuri S.S.V.P.,National Center for Laboratory Animal science | Putcha U.K.,National Institute of Nutrition ICMR | Veettil G.N.,National Center for Laboratory Animal science | Ayyalasomayajula V.,National Center for Laboratory Animal science
Indian Journal of Medical Research | Year: 2016

Background & objectives: Adipose tissue dysfunction in obesity is linked to the development of type 2 diabetes and cardiovascular diseases. We studied the differential gene expression in retroperitoneal adipose tissue of a novel obese rat model, WNIN/Ob, to understand the possible underlying transcriptional changes involved in the development of obesity and associatedcomorbidities in this model. Methods: Four month old, male WNIN/Ob lean and obese rats were taken, blood was collected and tissues were dissected. Body composition analysis and adipose tissue histology were performed. Global gene expression in retroperitoneal adipose tissue of lean and obese rats was studied by microarray using Affymetrix GeneChips. Results: One thousand and seventeen probe sets were downregulated and 963 probe sets were upregulated (more than two-fold) in adipose tissue of WNIN/Ob obese rats when compared to that of lean rats. Small nucleolar RNA (SnoRNA) made most of the underexpressed probe sets, whereas immune system-related genes werethe most overexpressed in the adipose tissues of obese rats. Genes coding for cytoskeletal proteinswere downregulated, whereas genes related to lipid biosynthesis were elevated in the adipose tissue of obese rats. Interpretation & conclusions: Majority of the altered genes and pathways in adipose tissue of WNIN/ Ob obese rats were similar to the observations in other obese animal models and human obesity. Based on these observations, it is proposed that WNIN/Ob obese rat model may be a good model to study the mechanisms involved in the development of obesity and its comorbidities. Downregulation of SnoRNA appears to be a novel feature in this obese rat model. © 2016, Indian Council of Medical Research. All rights reserved.


Sakamuri V.P.S.,National Institute of Nutrition | Ananthathmakula P.,National Institute of Nutrition | Veettil G.N.,National Center for Laboratory Animal science | Ayyalasomayajula V.,National Institute of Nutrition
Nutrition Journal | Year: 2011

Background: 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet) on 11-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods. Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype) were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11-HSD1 activity was assayed in liver and visceral fat. Results: Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein (C/EBP), the main transcription factor essential for the expression of 11-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor (LXR), a nuclear transcription factor which is known to downregulate 11-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions: This study suggests that chronic consumption of vitamin A-enriched diet decreases 11-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly contribute to visceral fat loss in these obese rats. Studying the role of various nutrients on the regulation of 11-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance. © 2011 Sakamuri et al; licensee BioMed Central Ltd.


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.


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.


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.


Prasad S.S.V.,National Institute of Nutrition | Prashanth A.,National Institute of Nutrition | Kumar C.P.,National Institute of Nutrition | Reddy S.J.,National Institute of Nutrition | And 2 more authors.
Lipids in Health and Disease | Year: 2010

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and plays an important role in the development of obesity and metabolic syndrome. 11β-HSD1 activity is lower in liver and higher in omental adipose tissue of obese rodent models like obese zucker rats, Ob/Ob and db/db mice. Here, we report the 11β-HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob strain, a new genetic rat model of obesity. 11β-HSD1 activity in liver, omental and subcutaneous adipose tissues of 3 month-old male WNIN/Ob lean and obese rats was assayed. As observed in other rodent models, 11β-HSD1 activity was lower in liver and higher in omental adipose tissue. In contrast to other rodent obese models, WNIN/Ob obese rats had elevated 11β-HSD1 activity in subcutaneous adipose tissue, which is in line with the observation in human obesity. Here, we conclude that dysregulation of 11β-HSD1 in WNIN/Ob obese rat model is identical to human obesity, which makes it an excellent model for studying the effect of 11β-HSD1 inhibitors in ameliorating obesity and metabolic syndrome. © 2010 Prasad et al; licensee BioMed Central Ltd.


Harishankar N.,National Center for Laboratory Animal science | Kumar P.U.,National Institute of Nutrition | Sesikeran B.,National Institute of Nutrition | Giridharan N.,National Center for Laboratory Animal science
Indian Journal of Medical Research | Year: 2011

Background & objectives: WNIN/Ob (obese and euglycaemic) and WNIN/GR-Ob (obesity with impaired glucose tolerance), were isolated and established from Wistar rat stock (WNIN). Both strains showed physical, physiological and biochemical indices related to obesity. We present here haematology, histology and pathophysiological changes between the phenotypes of these strains, lean (+/+), carrier (+/-) and obese (-/-). Methods: A total of 72 animals of equal gender consisting of three phenotypes were used for the study. Haematology, organ weights were measured and histopathology of the tissues studied using standard procedures. In 12 lean and obese rats (equal gender) of WNIN/GR-Ob group morphometry of pancreatic islets was done immunohistochemically (IHC). Results: Obese rats of both the strains showed normal haematology (except low platelet count), but exhibited changes in the organ weights and in histopathology in organs like liver, kidney, brain and testis/ovary. Hyperplasia of adipocytes was seen in obese rats as compared to lean and carrier. IHC of obese rat pancreas showed that both islet density and volume were significantly (P<0.05) increased compared to lean littermates. Interpretation & conclusions: The histological and pathophysiological changes seen in these mutants were in tune with obese phenotype exhibited by these animals.


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.


PubMed | National Center for Laboratory Animal science and National Institute of Nutrition ICMR
Type: Journal Article | Journal: Nutrition & metabolism | Year: 2014

Previously, we reported that vitamin A-enriched diet (129mg/kg diet) intake reduces the adiposity development in obese rats of WNIN/Ob strain. Here, we hypothesize that dose lesser than 129mg of vitamin A/kg diet would also be effective in ameliorating the development of obesity in these rats.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 2.6mg (control group), 26mg, 52mg and 129mg vitamin A/kg diet as retinyl palmitate for 20weeks. Body composition and morphological analysis of brown adipose tissue (BAT) was analyzed. Expression of uncoupling protein 1 (UCP1), retinoic acid receptor (RAR) and retinoid X receptor (RXR) in BAT and levels of Bcl2 and Bax in epididymal white adipose tissue (eWAT) were determined by immunoblotting.Vitamin A supplementation to obese rats at doses of 52 and 129mg/kg diet showed reduced body weight gain and adiposity compared to control diet-fed obese rats receiving 2.6mg of vitamin A/kg diet. In BAT of obese rats, vitamin A supplementation at doses of 26 and 52mg of vitamin A/kg diet resulted in increased UCP1 expression with concomitant decrease in RAR and RXR 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 52mg of vitamin A/kg diet. Also, obese rats fed on 52mg/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.In conclusion, chronic consumption of 52mg 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.


PubMed | National Center for Laboratory Animal science and National Institute of Nutrition ICMR
Type: Journal Article | Journal: The Indian journal of medical research | Year: 2017

Adipose tissue dysfunction in obesity is linked to the development of type 2 diabetes and cardiovascular diseases. We studied the differential gene expression in retroperitoneal adipose tissue of a novel obese rat model, WNIN/Ob, to understand the possible underlying transcriptional changes involved in the development of obesity and associatedcomorbidities in this model.Four month old, male WNIN/Ob lean and obese rats were taken, blood was collected and tissues were dissected. Body composition analysis and adipose tissue histology were performed. Global gene expression in retroperitoneal adipose tissue of lean and obese rats was studied by microarray using Affymetrix GeneChips.One thousand and seventeen probe sets were downregulated and 963 probe sets were upregulated (more than two-fold) in adipose tissue of WNIN/Ob obese rats when compared to that of lean rats. Small nucleolar RNA (SnoRNA) made most of the underexpressed probe sets, whereas immune system-related genes werethe most overexpressed in the adipose tissues of obese rats. Genes coding for cytoskeletal proteinswere downregulated, whereas genes related to lipid biosynthesis were elevated in the adipose tissue of obese rats.Majority of the altered genes and pathways in adipose tissue of WNIN/Ob obese rats were similar to the observations in other obese animal models and human obesity. Based on these observations, it is proposed that WNIN/Ob obese rat model may be a good model to study the mechanisms involved in the development of obesity and its comorbidities. Downregulation of SnoRNA appears to be a novel feature in this obese rat model.

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