Publications by authors named "Ayyalasomayajula Vajreswari"

25 Publications

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Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease: Omega-3 long-chain polyunsaturated fatty acids.

World J Clin Cases 2021 Nov;9(31):9333-9349

Department of Biochemistry, National Institute of Nutrition, Hyderabad 500007, Telangana, India.

Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders, including obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of disorders, and starts with simple steatosis, progresses to non-alcoholic steatohepatitis, and then advances to fibrosis, cirrhosis and finally, hepatocellular carcinoma, due to perpetual cycles of insults caused by inflammation and other cellular stress. Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019 (COVID-19), and patients with COVID-19 have a higher liver injury and mortality. Although the exact cause or mechanism is not known, inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is known to be associated with higher mortality among COVID-19 patients. Therefore, the COVID-19 pandemic seems to be a major concern in NAFLD patients, who have contracted SARS-CoV-2 infection and develop COVID-19. This is evident in patients at any stage of the NAFLD spectrum, as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD. Thus, there is a need for resolution of the inflammatory cytokine storm in these patients. A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) in NAFLD conditions, due to their anti-inflammatory, immunomodulatory and anti-viral properties. Therefore, intervention with ω-3 LCPUFA, an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression. Although there are challenges in implementation, optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics; NAFLD and COVID-19 at least in this subset of patients.
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http://dx.doi.org/10.12998/wjcc.v9.i31.9333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610854PMC
November 2021

Carrot Juice Consumption Reduces High Fructose-Induced Adiposity in Rats and Body Weight and BMI in Type 2 Diabetic Subjects.

Nutr Metab Insights 2021 15;14:11786388211014917. Epub 2021 Jul 15.

Division of Lipid Biochemistry, ICMR-National Institute of Nutrition, Hyderabad, Telangana, India.

Nutritional intervention is a key strategy in the control and management of non-communicable diseases. Here, initially, we evaluated the effects of carrot juice (CJ) on some of the physical and biochemical parameters in rats fed with high-fructose diet, then in type 2 diabetic subjects. For the animal study, weanling male Wistar rats were given control (n = 6) or high fructose (HFr; n = 24) diet for 8 weeks. Then, the HFr group rats were subdivided into 4 groups (n = 6 in each) and continued either on HFr diet or shifted to control diet, with or without CJ (0.3 mg β-carotene) ingestion orally for 8 weeks. At the end, the ingestion of CJ reversed the HFr-induced adiposity (23 ± 1.6 vs 18 ± 1.1,  = .038), hypertriglyceridemia (182 ± 18.2 vs 90 ± 10.5 mg/dL, <0.001), and hyperinsulinemia (81 ± 14.7 vs 40 ± 7.5 µU/mL,  = .014), while increased the retinol levels in liver (240 ± 38.4 vs 492 ± 61.2 µg/g,  = .002) and adipose tissue (1.8 ± 0.09 vs 2.5 ± 0.18 µg/g,  = .026). On the other hand, in the diabetic subjects (7 males and females each, n = 14) compared to their baseline, the daily consumption of 50 mL CJ (~2400 µg β-carotene) for 6 weeks significantly reduced the body weight (69.4 ± 4.13 vs 69.0 ± 4.09 kg,  = .014), BMI (27.4 ± 1.07 vs 27.2 ± 1.06 kg/m,  = .007), and fat% (33.4 ± 1.87 vs 31.9 ± 2.13,  = .029) with an increase in plasma β-carotene levels (0.21 ± 0.045 vs 0.45 ± 0.089 µmol/L,  = .044). Although CJ increased the glucose (145 ± 10.4 vs 165 ± 11.4 mg/dL,  = .039), insulin, and glycated hemoglobin levels remained unaltered. In conclusion, the consumption of carrot juice reversed the HFr-induced metabolic abnormalities in a rat model and decreased body weight and BMI of diabetic subjects.
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http://dx.doi.org/10.1177/11786388211014917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287410PMC
July 2021

Consumption of vitamin A-deficient diet elevates endoplasmic reticulum stress marker and suppresses high fructose-induced orexigenic gene expression in the brain of male Wistar rats.

Nutr Neurosci 2021 Apr 8:1-9. Epub 2021 Apr 8.

Lipid Biochemistry Division, ICMR-National Institute of Nutrition, Hyderabad, Telangana, India.

Objective: Here, we assessed the impact of vitamin A deficiency (both alone and in combination with fructose) on the retinol status, phospholipids fatty acid composition and pathways associated with the endoplasmic reticulum (ER) stress and energy homeostasis of the brain. For this purpose, weanling male Wistar rats were divided into four groups consisting of 8 rats each, except 16 for the second group and they received one of the following diets; control, vitamin A-deficient (VAD), high fructose (HFr) and HFr with VAD for 16 weeks, except half of the VAD diet-fed rats, were shifted to HFr diet, after 8 weeks period.

Results: The retinol content of the whole brain remained comparable across the groups, despite a significant reduction in the plasma at the end of VAD diet feeding. However, it suppressed the HFr-induced neuropeptide Y and agouti-related peptide, while rescuing the leptin receptor mRNA. Among ER stress markers, CCAAT/Enhancer-binding protein homologues protein levels were elevated significantly in the VAD diet-fed group. Further, the long-chain polyunsaturated fatty acid levels showed an increase in the brain phospholipids across the experimental groups, compared to that of the control.

Conclusion: Vitamin A deficiency causes ER stress in the brain, and retinol seems to play a regulatory role in the fructose-mediated transcriptional regulation of the genes involved in energy homeostasis.
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http://dx.doi.org/10.1080/1028415X.2021.1911048DOI Listing
April 2021

High-Fat Diet Elevates Liver Docosahexaenoic Acid Possibly through Over-Expression of Very Long-Chain Fatty Acid Elongase 2 in C57BL/6J Mice.

Int J Vitam Nutr Res 2019 Jul 8;89(1-2):62-72. Epub 2019 Apr 8.

1Lipid Biochemistry Division, National Institute of Nutrition, Jamai Osmania, Hyderabad, India.

The liver is the main site of lipid metabolism and vitamin A storage. Dietary factors are known to affect liver function, thereby leading to metabolic abnormalities. Here, we assessed the impact of long-term feeding of a high-fat diet on hepatic vitamin A status and lipid metabolism. For this purpose, 14 male and 14 female 35-day-old mice (strain C57BL/6J) were each divided into 2 groups of 7 animals and fed either a stock diet or a high-fat (HF) diet for 26 weeks. In addition to increased body weight/weight gain, the HF diet induced hypertriglyceridemia in both (p < 0.01). However, liver triglyceride levels were comparable among groups, which could be partly explained by unaltered expression of various lipogenic pathway proteins such as sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), microsomal triglyceride transfer protein (MTTP), and glycerol 3-phosphate acyl transferase (GPAT). On the other hand, hepatic retinol stores increased significantly in both sexes, whereas males displayed elevated circulatory retinol levels. Notably, long-term feeding of a HF diet elevated n-3 polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (DHA, C22:6) levels in the liver (p ≤ 0.001), which is in line with the over-expression of very long-chain fatty acid elongase 2 (ELOVL2) protein in both sexes of mice (p < 0.01). In conclusion, very long-term feeding of a HF diet increased hepatic retinol stores and induced hypertriglyceridemia. However, it had no effect on hepatic triglyceride accumulation, possibly due to increased DHA levels arising from the ELOVL2-mediated elongation pathway.
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http://dx.doi.org/10.1024/0300-9831/a000432DOI Listing
July 2019

Vitamin A Improves Hyperglycemia and Glucose-Intolerance through Regulation of Intracellular Signaling Pathways and Glycogen Synthesis in WNIN/GR-Ob Obese Rat Model.

Prev Nutr Food Sci 2017 Sep 30;22(3):172-183. Epub 2017 Sep 30.

Lipid Biochemistry Division, National Institute of Nutrition, Hyderabad, Telangana 500007, India.

Vitamin A and its metabolites modulate insulin resistance and regulate stearoyl-CoA desaturase 1 (SCD1), which are also known to affect insulin resistance. Here, we tested, whether vitamin A-mediated changes in insulin resistance markers are associated with SCD1 regulation or not. For this purpose, 30-week old male lean and glucose-intolerant obese rats of WNIN/GR-Ob strain were given either a stock or vitamin A-enriched diet, i.e. 2.6 mg or 129 mg vitamin A/kg diet, for 14 weeks. Compared to the stock diet, vitamin A-enriched diet feeding improved hyperglycemia and glucose-clearance rate in obese rats and no such changes were seen in lean rats receiving identical diets. These changes were corroborated with concomitant increase in circulatory insulin and glycogen levels of liver and muscle (whose insulin signaling pathway genes were up-regulated) in obese rats. Further, the observed increase in muscle glycogen content in these obese rats could be explained by increased levels of the active form of glycogen synthase, the key regulator of glycogen synthesis pathway, possibly inactivated through increased phosphorylation of its upstream inhibitor, glycogen synthase kinase. However, the unaltered hepatic SCD1 protein expression (despite decreased mRNA level) and increased muscle-SCD1 expression (both at gene and protein levels) suggest that vitamin A-mediated changes on glucose metabolism are not associated with SCD1 regulation. Chronic consumption of vitamin A-enriched diet improved hyperglycemia and glucose-intolerance, possibly, through the regulation of intracellular signaling and glycogen synthesis pathways of muscle and liver, but not associated with SCD1.
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http://dx.doi.org/10.3746/pnf.2017.22.3.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642798PMC
September 2017

Transcriptome profiling of visceral adipose tissue in a novel obese rat model, WNIN/Ob & its comparison with other animal models.

Indian J Med Res 2016 Sep;144(3):409-423

Department of Biochemistry, National Institute of Nutrition (ICMR), Hyderabad, India.

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.
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http://dx.doi.org/10.4103/0971-5916.198667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320847PMC
September 2016

Chronic vitamin A-enriched diet feeding regulates hypercholesterolaemia through transcriptional regulation of reverse cholesterol transport pathway genes in obese rat model of WNIN/GR-Ob strain.

Indian J Med Res 2016 Aug;144(2):238-244

Division of Lipid Biochemistry, National Institute of Nutrition, Hyderabad, India.

Background & Objectives: Hepatic scavenger receptor class B1 (SR-B1), a high-density lipoprotein (HDL) receptor, is involved in the selective uptake of HDL-associated esterified cholesterol (EC), thereby regulates cholesterol homoeostasis and improves reverse cholesterol transport. Previously, we reported in euglycaemic obese rats (WNIN/Ob strain) that feeding of vitamin A-enriched diet normalized hypercholesterolaemia, possibly through hepatic SR-B1-mediated pathway. This study was aimed to test whether it would be possible to normalize hypercholesterolaemia in glucose-intolerant obese rat model (WNIN/GR/Ob) through similar mechanism by feeding identical vitamin A-enriched diet.

Methods: In this study, 30 wk old male lean and obese rats of WNIN/GR-Ob strain were divided into two groups and received either stock diet or vitamin A-enriched diet (2.6 mg or 129 mg vitamin A/kg diet) for 14 wk. Blood and other tissues were collected for various biochemical analyses.

Results: Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized abnormally elevated plasma HDL-cholesterol (HDL-C) levels in obese rats as compared to stock diet-fed obese groups. Further, decreased free cholesterol (FC) and increased esterified cholesterol (EC) contents of plasma cholesterol were observed, which were reflected in higher EC to FC ratio of vitamin A-enriched diet-fed obese rats. However, neither lecithin-cholesterol acyltransferase (LCAT) activity of plasma nor its expression (both gene and protein) in the liver were altered. On the contrary, hepatic cholesterol levels significantly increased in vitamin A-enriched diet fed obese rats. Hepatic SR-B1 expression (both mRNA and protein) remained unaltered among groups. Vitamin A-enriched diet fed obese rats showed a significant increase in hepatic low-density lipoprotein receptor mRNA levels, while the expression of genes involved in HDL synthesis, namely, ATP-binding cassette protein 1 (ABCA1) and apolipoprotein A-I, were downregulated. No such response was seen in vitamin A-supplemented lean rats as compared with their stock diet-fed lean counterparts.

Interpretation & Conclusions: Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized HDL-C levels, possibly by regulating pathways involved in HDL synthesis and degradation, independent of hepatic SR-B1 in this glucose-intolerant obese rat model.
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http://dx.doi.org/10.4103/0971-5916.195038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206875PMC
August 2016

Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats.

Prev Nutr Food Sci 2016 Sep 30;21(3):171-180. Epub 2016 Sep 30.

Lipid Biochemistry Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.
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http://dx.doi.org/10.3746/pnf.2016.21.3.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063201PMC
September 2016

Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats.

J Sci Food Agric 2017 Mar 25;97(5):1582-1591. Epub 2016 Aug 25.

Lipid Biochemistry Division, National Institute of Nutrition, Jamai Osmania, Hyderabad, 500007, India.

Background: Adipose tissue, an endocrine organ, plays a vital role not only in energy homeostasis, but also in the development and/or progression of various metabolic diseases, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), via several factors and mechanisms, including inflammation. This study tested, whether carrot juice administration affected the adipose tissue development and its inflammatory status in a high fructose diet-induced rat model. For this purpose, male weanling Wistar rats were divided into four groups and fed either control or high fructose diet of AIN-93G composition with or without carrot juice ingestion for an 8 week period.

Results: Administration of carrot juice did not affect the adiposity and cell size of visceral fat depot; retroperitoneal white adipose tissue (RPWAT), which was corroborated with unaltered expression of genes involved in adipogenic and lipogenic pathways. However, it significantly reduced the high fructose diet-induced elevation of plasma free fatty acid (FFA) (P ≤ 0.05), macrophage chemoattractant protein 1 (MCP1) (P ≤ 0.01) and high sensitive C-reactive protein (hsCRP) (P ≤ 0.05) levels.

Conclusion: Carrot juice administration attenuated the high fructose diet-induced elevation of levels of circulatory FFA and pro-inflammatory mediators; MCP1 and hsCRP without affecting the adiposity and cell size of visceral fat depot; RPWAT. © 2016 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.7906DOI Listing
March 2017

Vitamin A deficiency suppresses high fructose-induced triglyceride synthesis and elevates resolvin D1 levels.

Biochim Biophys Acta 2016 Mar 18;1861(3):156-65. Epub 2015 Nov 18.

Lipid Biochemistry Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India. Electronic address:

Background/aims: Vitamin A and its metabolites are known to regulate lipid metabolism. However so far, no study has assessed, whether vitamin A deficiency per se aggravates or attenuates the development of non-alcoholic fatty liver disease (NAFLD). Therefore, here, we tested the impact of vitamin A deficiency on the development of NAFLD.

Methods: Male weanling Wistar rats were fed one of the following diets; control, vitamin A-deficient (VAD), high fructose (HFr) and VAD with HFr (VADHFr) of AIN93G composition, for 16weeks, except half of the VAD diet-fed rats were shifted to HFr diet (VAD(s)HFr), at the end of 8(th) week.

Results: Animals fed on VAD diet with HFr displayed hypotriglyceridemia (33.5mg/dL) with attenuated hepatic triglyceride accumulation (8.2mg/g), compared with HFr diet (89.5mg/dL and 20.6mg/g respectively). These changes could be partly explained by the decreased activity of glycerol 3-phosphate dehydrogenase (GPDH) and the down-regulation of stearoyl CoA desaturase 1 (SCD1), both at gene and protein levels, the key determinants of triglyceride biosynthesis. On the other hand, n-3 long chain polyunsaturated fatty acid, docosahexaenoic acid and its active metabolite; resolvin D1 (RvD1) levels were elevated in the liver and plasma of VAD diet-fed groups, which was negatively associated with triglyceride levels. All these factors confer vitamin A deficiency-mediated protection against the development of hepatic steatosis, which was also evident from the group shifted from VAD to HFr diet.

Conclusions: Vitamin A deficiency attenuates high fructose-induced hepatic steatosis, by regulating triglyceride synthesis, possibly through GPDH, SCD1 and RvD1.
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http://dx.doi.org/10.1016/j.bbalip.2015.11.005DOI Listing
March 2016

Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model.

Indian J Med Res 2015 Mar;141(3):275-84

Lipid Biochemistry Division, National Institute of Nutrition (ICMR), Hyderabad, India.

During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life). Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation) in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442325PMC
http://dx.doi.org/10.4103/0971-5916.156554DOI Listing
March 2015

Chronic vitamin A-enriched diet feeding induces body weight gain and adiposity in lean and glucose-intolerant obese rats of WNIN/GR-Ob strain.

Exp Physiol 2015 Nov 20;100(11):1352-61. Epub 2015 Oct 20.

Lipid Biochemistry Division, National Institute of Nutrition, Jamai-Osmania, Hyderabad, 500 007, India.

New Findings: What is the central question of this study? Previously, we reported that chronic feeding of a vitamin A-enriched diet to euglycaemic obese rats (WNIN/Ob) ameliorated obesity. Does this diet exert similar effects even with a different genetic background, i.e. obese rats of the WNIN/GR-Ob strain with impaired glucose tolerance? What is the main finding and its importance? Vitamin A-enriched diet aggravated weight gain and adiposity/obesity in both lean and glucose-intolerant obese rats of the WNIN/GR-Ob strain. Therefore, the role of genetic factors and their regulation by nutrients in determining health and disease conditions assumes greater significance in experimental and clinical research. Vitamin A and its metabolites are key regulators of the development of adipose tissue and its associated metabolic complications. Here, we tested, in a glucose-intolerant obese rat model (the WNIN/GR-Ob stain), whether feeding a vitamin A-enriched diet alters adiposity and its associated changes. For this purpose, 30-week-old male lean and obese rats were divided into two groups and received either stock diet or vitamin A-enriched diet [2.6 or 129 mg vitamin A (kg diet)(-1) , respectively] for 14 weeks. At the end, feeding of the vitamin A-enriched diet resulted in increased body weight gain/obesity and retroperitoneal white adipose tissue (RPWAT) in both lean and obese rats of the WNIN/GR-Ob strain, when compared with their respective control animals receiving stock diet, without affecting food intake. An improvement in hypertriglyceridaemia and circulatory non-esterified fatty acid levels and unaltered hepatic fatty acid oxidative and triglyceride secretory pathway proteins with vitamin A-enriched diet feeding are suggestive of enhanced hepatic clearance of circulatory lipids, resulting in increased hepatic triglyceride accumulation. Transcriptional analysis of RPWAT showed that feeding the vitamin A-enriched diet augmented the expression of adipogenic/adipose tissue-specific genes; peroxisome proliferator-activated receptor-γ, stearoyl CoA desaturase 1, retinol saturase, leptin and lipoprotein lipase and vitamin A metabolic pathway genes; retinoic acid receptors, retinoid X receptors and cytochrome P450 26B1. Besides, RPWAT-lipoprotein lipase-mediated clearance of triglyceride could also have contributed to increased adiposity and improved hypertriglyceridaemia. In conclusion, chronic feeding of vitamin A-enriched diet induces weight gain and adiposity in both lean and obese rats of the WNIN/GR-Ob strain, possibly through transcriptional regulation of key adipogenic pathway genes of RPWAT, but improves dyslipidaemia.
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http://dx.doi.org/10.1113/EP085027DOI Listing
November 2015

Mitochondriogenesis and apoptosis: possible cause of vitamin A-mediated adipose loss in WNIN/Ob-obese rats.

Nutr Metab (Lond) 2014 25;11(1):45. Epub 2014 Sep 25.

Department of Lipid Biochemistry, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, 500 007 Andhra Pradesh India.

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.
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http://dx.doi.org/10.1186/1743-7075-11-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190477PMC
October 2014

Vitamin A-enriched diet modulates reverse cholesterol transport in hypercholesterolemic obese rats of the WNIN/Ob strain.

J Atheroscler Thromb 2014 6;21(11):1197-207. Epub 2014 Aug 6.

Department of Lipid Biochemistry, National Institute of Nutrition (ICMR).

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 acyltransferase 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.
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http://dx.doi.org/10.5551/jat.22186DOI Listing
July 2015

Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats.

PLoS One 2012 17;7(12):e50216. Epub 2012 Dec 17.

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderabad, Andhra Pradesh, India.

Background: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX) on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity.

Methodology/principal Findings: Subcutaneous injection of CBX (50 mg/kg body weight) or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment). Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment.

Conclusions/significance: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050216PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524236PMC
June 2013

Vitamin A supplementation ameliorates obesity-associated retinal degeneration in WNIN/Ob rats.

Nutrition 2013 Jan 2;29(1):298-304. Epub 2012 Oct 2.

Department of Biochemistry, National Institute of Nutrition, Hyderabad, India.

Objective: Obesity is associated with various health afflictions, including ocular complications such as diabetic retinopathy, high intraocular pressure, cataracts, and macular degeneration. We previously reported progressive retinal degeneration after the onset of obesity in the spontaneously obese rat (WNIN/Ob) model. In the present study, we investigated vitamin A supplementation to ameliorate obesity-associated retinal degeneration in the WNIN/Ob rat.

Methods: Five-month-old male WNIN/Ob obese (O) and lean (L) control rats were fed with vitamin A 2.6 mg (L/O-I), 26 mg (L/O-II), 52 mg (L/O-III), and 129 mg (L/O-IV) per kilogram of diet as retinyl palmitate for 4 mo 2 wk. Retinal morphology and retinal gene expression were assessed by histologic, immunohistochemical, and real-time polymerase chain reaction methods.

Results: Supplementation of vitamin A at 26 or 52 mg significantly modulated the expression of retinal genes in the O but not in the L phenotype. Vitamin A supplementation significantly upregulated the expression of genes, such as rhodopsin, rod arrestin, phosphodiesterase, transducins, and fatty acid elongase-4, that were otherwise downregulated in O rat retina. The expression of glial fibrillary acidic protein was downregulated by vitamin A feeding in O rat retina. The immunohistochemical and histologic findings corroborated the gene expression data. The effects were significant at a 26- or 52-mg dose of vitamin A.

Conclusion: Vitamin A supplementation alleviated obesity-associated retinal degeneration in the WNIN/Ob rat.
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http://dx.doi.org/10.1016/j.nut.2012.06.006DOI Listing
January 2013

Chronic consumption of trans-fat-rich diet increases hepatic cholesterol levels and impairs muscle insulin sensitivity without leading to hepatic steatosis and hypertriglyceridemia in female Fischer rats.

Ann Nutr Metab 2011 Oct 9;58(4):272-80. Epub 2011 Sep 9.

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.

Background: The impact of industrial trans fatty acids (TFAs) on lipid metabolism and health remains elusive.

Methods: We compared the effect of long-term (52 weeks) ingestion of 10% partially hydrogenated vegetable oil, providing 4.2% of total energy from TFAs, on hepatic lipid metabolism and muscle insulin sensitivity in weanling female Fischer rats with that of palmolein (monounsaturated fatty acid, MUFA), sunflower (n-6 polyunsaturated fatty acid, PUFA), and a blend of sunflower and fish oil (n-3 PUFA).

Results: The proportion of plasma high-density lipoprotein cholesterol in total cholesterol and reverse cholesterol transport-associated protein expressions were similar in all the groups. Despite higher lipogenic-pathway protein levels, steatosis or hypertriglyceridemia was not observed in TFA-fed rats. Though TFA ingestion had no effect on fasting plasma glucose, insulin levels or oral glucose tolerance, it significantly decreased muscle insulin-stimulated glucose uptake as compared to PUFAs. Further, TFA ingestion increased adipose tissue retinol-binding protein 4 mRNA as compared to PUFAs (n-6 or n-3). The effects of MUFA (oleic acid) on all these parameters were comparable to those observed for TFAs.

Conclusions: Compared to PUFA-rich diets, chronic consumption of a TFA-rich diet did not lead to steatosis or hypertriglyceridemia; however, it significantly impaired muscle insulin sensitivity, while no changes were found in the oral glucose tolerance test.
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http://dx.doi.org/10.1159/000331215DOI Listing
October 2011

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats.

Nutr J 2011 Jun 23;10:70. Epub 2011 Jun 23.

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderabad-500 604, Andhra Pradesh, India.

Background: 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-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 11β-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 11β-HSD1 activity was assayed in liver and visceral fat.

Results: Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα), the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα), a nuclear transcription factor which is known to downregulate 11β-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 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-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 11β-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance.
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http://dx.doi.org/10.1186/1475-2891-10-70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142207PMC
June 2011

A novel genetically-obese rat model with elevated 11 beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue.

Lipids Health Dis 2010 Nov 17;9:132. Epub 2010 Nov 17.

Department of Biochemistry, National Institute of Nutrition, Jamai Osmania PO, Hyderabad-500 604, Andhra Pradesh, India.

11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and plays an important role in the development of obesity and metabolic syndrome. 11 β-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 11 β-HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob strain, a new genetic rat model of obesity. 11 β-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, 11 β-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 11 β-HSD1 activity in subcutaneous adipose tissue, which is in line with the observation in human obesity. Here, we conclude that dysregulation of 11 β-HSD1 in WNIN/Ob obese rat model is identical to human obesity, which makes it an excellent model for studying the effect of 11 β-HSD1 inhibitors in ameliorating obesity and metabolic syndrome.
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http://dx.doi.org/10.1186/1476-511X-9-132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161380PMC
November 2010

Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue.

Lipids Health Dis 2010 Oct 8;9:111. Epub 2010 Oct 8.

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderabad-500 604, Andhra Pradesh, India.

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome.
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http://dx.doi.org/10.1186/1476-511X-9-111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959202PMC
October 2010

Fatty acid desaturation index correlates with body mass and adiposity indices of obesity in Wistar NIN obese mutant rat strains WNIN/Ob and WNIN/GR-Ob.

Nutr Metab (Lond) 2009 Jun 11;6:27. Epub 2009 Jun 11.

Biochemistry Division, National Institute of Nutrition, Jamai Osmania, Hyderabad-500 604, India.

Background: Microsomal stearoyl-CoA desaturase1 (SCD1) is the rate limiting enzyme involved in the biosynthesis of monounsaturated fatty acids (MUFAs); palmitoleic (16:1) and oleic (18:1) acid from their respective substrates palmitic (16:0) and stearic (18:0) acids. The ratio of 18:1 to 18:0 has been implicated in the regulation membrane fluidity and function. SCD1 is abundantly expressed in obese humans as well as rodent models. However, no studies have correlated the fatty acid desaturation index (16:1/16:0 and 18:1/18:0), an indicator of SCD1 activity with the markers of obesity in terms of body mass index (BMI) and adiposity index (AI). Therefore, here, we attempted to relate the fatty acid desaturation index with BMI and AI in Wistar NIN-obese mutant rat strains namely, WNIN/Ob and WNIN/GR-Ob (with impaired glucose tolerance).

Methods: For this purpose, 200 days old male 6 lean and 6 obese rats of both strains were taken. Fatty acid composition was analyzed in plasma, various tissues such as liver, white adipose tissues (retroperitoneal, epididymal, omental, and subcutaneous) and brown adipose tissue.

Results: Fatty acid composition data showed significant increase in palmitoleic (16:1) and oleic (18:1) acid levels, which were reflected in increased desaturation index (16:1/16:0 and 18:1/18:0) in plasma and all the tissues of obese rats of both strains, when compared with their respective age and sex-matched lean rats. Further, we found a strong positive correlation between desaturation index, BMI and AI in plasma and most of the tissues analyzed.

Conclusion: So far, plasma Δ⁹ desaturation index has been well correlated with hypertriglyceridemia and we, by employing two models of obesity namely, WNIN/Ob and WNIN/GR-Ob, have shown Δ⁹ desaturation index of plasma correlated with physical markers of obesity such as BMI and AI. In conclusion, Δ⁹ desaturation index may serve as a potential sensitive biochemical marker to assess the degree of obesity and impact of therapeutic/nutritional interventions to combat obesity, along with other indicators.
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http://dx.doi.org/10.1186/1743-7075-6-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704216PMC
June 2009

Impact of feeding polyunsaturated fatty acids on cholesterol metabolism of dyslipidemic obese rats of WNIN/GR-Ob strain.

Atherosclerosis 2009 May 2;204(1):136-40. Epub 2008 Sep 2.

Department of Biochemistry, National Institute of Nutrition (ICMR), Hyderabad 500604, Andhra Pradesh, India.

Dietary fatty acids are known to play an important role in the development as well as prevention of dyslipidemia. In this study, we evaluated the impact of feeding polyunsaturated fatty acids (PUFAs) for a period of 4 months on various aspects of cholesterol metabolism in genetically obese mutant rats of WNIN/GR-Ob strain. Based on their phenotype, lean and obese rats were divided into two groups, A and B respectively, and further subdivided depending on the type of dietary fat. Control groups of rats (AI and BI), were fed on 4% groundnut oil, which was replaced by safflower oil; n-6 PUFA diet (AII and BII) or oil blend of safflower and soybean oil, n-6 and n-3 PUFA diet (AIII and BIII) in the experimental groups. It was observed that feeding of diets with n-6 PUFA or a combination of n-6 and n-3 PUFAs resulted in marked elevation of plasma levels of total as well as HDL cholesterol and triglycerides in obese rats (BII and BIII), as compared to the control group (BI). Further, plasma HDL fraction of obese rats had elevated apolipoprotein E (apo E), while apo A1 levels remained unaltered. Increased lecithin: cholesterol acyltransferase (LCAT) activity and cholesteryl ester (CE) levels in the plasma and enhanced expression of hepatic scavenger receptor class B type1 (SR-B1) were also observed in PUFA-fed obese rats (BII and BIII). However, there was no change in hepatic ATP-binding cassette transporter protein A1 (ABCA1) levels in the obese rats fed on PUFA rich diets. Intriguingly, though these changes favor efficient removal of cholesterol from peripheral tissues, its esterification and enhanced clearance through reverse cholesterol transport (RCT); plasma HDL-C remained higher in these genetically dyslipidemic obese rats, thereby pointing at yet unknown mechanisms, involved in cholesterol homeostasis, which need to be studied.
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http://dx.doi.org/10.1016/j.atherosclerosis.2008.08.021DOI Listing
May 2009

Impact of vitamin A on high-density lipoprotein-cholesterol and scavenger receptor class BI in the obese rat.

Obesity (Silver Spring) 2007 Feb;15(2):322-9

Department of Biochemistry, National Institute of Nutrition, Hyderabad, India.

Objective: Scavenger receptor class BI (SR-BI), authentic high-density lipoprotein (HDL) receptors expressed in liver, are known to play an important role in HDL-cholesterol (C) metabolism and reverse cholesterol transport. Interestingly, obese rats of WNIN/Ob strain have abnormally elevated levels of serum HDL-C compared with their lean counterparts. Based on the well-established role of SR-B1 in HDL-C metabolism, it was hypothesized that these obese rats may have an underexpression of hepatic SR-B1 receptors. In view of the significant role of vitamin A in energy expenditure and obesity, we also tested whether vitamin A supplementation can correct abnormal HDL-C metabolism.

Research Methods And Procedures: To test this hypothesis, 7-month-old male lean and obese rats of WNIN/Ob strain were divided into two groups; each group was subdivided into two subgroups consisting of six lean and six obese rats and received diets containing either 2.6 or 129 mg vitamin A/kg diet for 2 months.

Results: At the end, obese rats receiving normal levels of vitamin A diet showed high serum HDL-C and lower hepatic SR-BI expression levels compared with lean counterparts. Furthermore, chronic dietary vitamin A supplementation resulted in overexpression of hepatic SR-BI receptors (protein and gene) with concomitant reduction in serum HDL-C levels in obese rats.

Discussion: Thus, our observations highlight the role of vitamin A in reverse cholesterol transport through up-regulation of hepatic SR-BI receptors and, thereby, HDL-C homeostasis in obese rats of WNIN/Ob strain.
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http://dx.doi.org/10.1038/oby.2007.534DOI Listing
February 2007

Chronic dietary vitamin A supplementation regulates obesity in an obese mutant WNIN/Ob rat model.

Obesity (Silver Spring) 2006 Jan;14(1):52-9

Department of Biochemistry, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad 500 007, Andra Pradesh, India.

Objective: To understand the possible role of chronic dietary high vitamin A supplementation in body weight regulation and obesity using a novel WNIN/Ob obese rat model developed at the National Centre for Laboratory Animal Sciences of National Institute of Nutrition, India.

Research Methods And Procedures: Thirty-six 7-month-old male rats of lean, carrier, and obese phenotypes were broadly divided into two groups; each group was subdivided into three subgroups consisting of six lean, six carrier, and six obese rats and received diets containing either 2.6 or 129 mg vitamin A/kg of diet for 2 months. Body weight gain, food intake, and weights of various organs were recorded. Adiposity index and BMI were calculated. Serum and liver retinol and brown adipose tissue (BAT)-uncoupling protein1 (UCP1) mRNA expression levels were quantified.

Results: Chronic feeding of high but non-toxic doses of vitamin A through diet significantly reduced (P < or = 0.05) body weight gain, adiposity index, and retroperitoneal white adipose tissue mass (without affecting food intake) in obese rats compared with their lean and carrier counterparts. In general, vitamin A treatment significantly improved hepatic retinol stores (P < or = 0.05) in all phenotypes without affecting serum free retinol levels. However, augmented BAT-UCP1 expression was observed only in carrier and obese rats (whose basal expression was low).

Discussion: Our data suggest that chronic dietary vitamin A supplementation at high doses effectively regulates obesity in obese phenotype of the WNIN/Ob strain, possibly through up-regulation of the BAT-UCP1 gene and associated adipose tissue loss. However, in vitamin A-supplemented lean and carrier rats, changes in adiposity could not be related to BAT-UCP1 expression levels.
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http://dx.doi.org/10.1038/oby.2006.7DOI Listing
January 2006

Effect of altered dietary n-6-to-n-3 fatty acid ratio on erythrocyte lipid composition and membrane-bound enzymes.

J Nutr Sci Vitaminol (Tokyo) 2002 Oct;48(5):365-70

National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderbad-500007, A.P. India.

Three experimental diets with varied n-6-to-n-3 fatty acid ratios (120, 40 and 8) were prepared by a suitable blending of safflower oil containing 72.5% linoleic (18:2 n-6) acid and non-detectable levels of alpha-linolenic (18:3 n-3) acid, and soybean oil having 56.1% linoleic (18:2 n-6) acid and 7.9% alpha-linolenic (18:3 n-3) acid. These diets were fed to weanling female Wistar/NIN (inbred) rats for 16 wk to assess the impact of altered dietary n-6-to-n-3 fatty acid ratio on erythrocyte membrane (EMS) cholesterol, phospholipids, fatty acid composition and activities of membrane-bound enzymes such as Na+,K+-ATPase, Ca2+, Mg2+-ATPase and acetylcholinesterase. Activities of total and ouabain-sensitive-ATPases were significantly higher in the erythrocyte membranes of rats fed diets with a n-6-to-n-3 fatty acid ratio of 40 compared to other groups, whereas the erythrocyte membrane-bound acetylcholinesterase was significantly different among the three groups. The highest and lowest activities for this enzyme were observed in the dietary groups with n-6-to-n-3 fatty acid ratios of 8 and 40 respectively. However, the EMS of rats fed diets with a n-6-to-n-3 fatty acid ratio of 40 alone had significantly higher Ca2+,Mg2+-ATPase compared to those of other two groups. Significant increases were observed in absolute amounts of cholesterol, phospholipids and molar ratio of cholesterol to phospholipids in the EMS of rats fed a diet with a very high 18:2 n-6-to-18:3 n-3 fatty acid ratio (120) as compared to those from the dietary group with 18:2 n-6-to-18:3 n-3 fatty acid ratio (40), which had the lowest levels of cholesterol, phospholipids and cholesterol-to-phospholipid molar ratio. On the other hand, the EMS from rats fed a diet with a very low n-6-to-n-3 fatty acid ratio (8) had significantly lower cholesterol and higher proportions of stearic (18:0), oleic (18:1 n-9), eicosapentaenoic (20:5 n-3), and docosahexaenoic acids, and a higher ratio of docosahexaenoic (22:6 n-3) acid-to-a-linoleic (18:3 n-3) acid compared to the EMS from a very high n-6-to-n-3 fatty acid ratio of 120. Although these changes in EM fatty acid profiles were expected of the respective dietary regimens, the observed changes in the activities of membrane-bound enzymes could have resulted from their interaction with membrane cholesterol, phospholipids and fatty acyl chains.
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http://dx.doi.org/10.3177/jnsv.48.365DOI Listing
October 2002
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