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

详细信息    查看全文

• 作者：Anamthathmakula Prashanth ; Shanmugam M Jeyakumar ; Lodhu Singotamu…
• 关键词：Vitamin A ; Dietary supplementation ; Uncoupling protein ; Thermogenesis ; Nuclear receptors ; Adipose tissue ; Apoptosis
• 刊名：Nutrition & Metabolism
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：11
• 期：1
• 全文大小：2,036 KB
• 参考文献：1. Cho, KJ, Moon, HE, Moini, H, Packer, L, Yoon, DY, Chung, AS (2003) α-Lipoic acid inhibits adipocyte differentiation by regulating proadipogenic transcription factors via mitogen-activated protein kinase pathways. J Bio Chem 278: pp. 34823-34833 CrossRef
  2. Palou, A, Serra, F, Bonet, ML, Picó, C (2000) Obesity: molecular bases of a multi-factorial problem. Eur J Nutr 39: pp. 127-144 CrossRef
  3. Prins, JB, O’Rahilly, S (1997) Regulation of adipose cell number in man. Clin Sci 92: pp. 3-11
  4. Jeyakumar, SM, Vajreswari, A, Giridharan, NV (2006) Chronic dietary vitamin A supplementation regulates obesity in an obese mutant WNIN/Ob rat model. Obesity 14: pp. 52-59 CrossRef
  5. Jeyakumar, SM, Vajreswari, A, Giridharan, NV (2008) Vitamin A regulates obesity in WNIN/Ob obese rat independent of stearoyl-CoA desaturase-1. Biochem Biophys Res Commun 370: pp. 243-247 CrossRef
  6. Harishankar, N, Vajreswari, A, Giridharan, NV (2011) WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain. Indian J Med Res 134: pp. 320-329 CrossRef
  7. Srigiridhar, K, Nair, KM, Subramanian, R, Singotamu, L (2001) Oral repletion of iron induces free radical mediated alterations in the gastrointestinal tract of rat. Mol Cell Biochem 219: pp. 91-98 CrossRef
  8. Gullicksen, PS, Hausman, DB, Dean, RG, Hartzell, DL, Baile, CA (2003) Adipose tissue cellularity and apoptosis after intracerebroventricular injections of leptin and 21?days of recovery in rats. Int J Obes Relat Metab Disord 27: pp. 302-312 CrossRef
  9. Jeyakumar, SM, Vajreswari, A, Sesikeran, B, Giridharan, NV (2005) Vitamin A supplementation induces adipose tissue loss through poptosis in lean but not in obese rats of the WNIN/Ob strain. J Mol Endocrinol 35: pp. 391-398 CrossRef
  10. Cannon, B, Nedergaard, J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84: pp. 277-359 CrossRef
  11. Atgié, C, Marette, A, Desautels, M, Tulp, O, Bukowiecki, LJ (1993) Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats. Am J Physiol 265: pp. C1674-C1680
  12. Kumar, MV, Sunvold, GD, Scarpace, PJ (1999) Dietary vitamin A supplementation in rats: suppression of leptin and induction of UCP1 mRNA. J Lipid Res 40: pp. 824-829
  13. Bonet, ML, Oliver, J, Picó, C, Felipe, F, Ribot, J, Cinti, S, Palou, A (2000) Opposite effects of vitamin A deficient diet-feeding and retinoic acid treatment on brown adipose tissue UCP1, UCP2 and leptin expression. J Endocrinol 166: pp. 511-517 CrossRef
  14. Ribot, J, Felipe, F, Bonet, ML, Palou, A (2001) Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression. Obes Res 9: pp. 500-509 CrossRef
  15. Ribot, J, Felipe, F, Bonet, ML, Palou, A (2004) Retinoic acid administration and vitamin A status modulate retinoid X receptor alpha and retinoic acid receptor alpha levels in mouse brown adipose tissue. Mol Cell Biochem 266: pp. 25-30 CrossRef
  16. Bonet, ML, Puigserver, P, Serra, F, Ribot, J, Vázquez, F, Pico, C, Palou, A (1997) Retinoic acid modulates retinoid X receptor alpha and retinoic acid receptor alpha levels of cultured brown adipocytes. FEBS Lett 406: pp. 196-200 CrossRef
  17. Murholm, M, Isidor, MS, Basse, AL, Winther, S, Sorensen, C, Skovgaard-Petersen, J, Nielsen, MM, Hansen, AS, Quistorff, B, Hansen, JB (2013) Ret
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Nutrition
  Metabolic Diseases
  Clinical Nutrition
  
• 出版者：BioMed Central
• ISSN：1743-7075

文摘

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.