title: Mitochondriogenesis and apoptosis: possible cause of vitamin A-mediated adipose loss in WNIN/Ob-obese rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Lipid Biochemistry, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Anamthathmakula
authors.initials: A
authors.lastname: Prashanth
authors.affiliation: Department of Lipid Biochemistry, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Shanmugam M
authors.initials: SM
authors.lastname: Jeyakumar
authors.affiliation: Ultra Structure Unit, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Lodhu
authors.initials: L
authors.lastname: Singotamu
authors.affiliation: National Center for Laboratory Animal Sciences (ICMR), Jamai-Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Nemani
authors.initials: N
authors.lastname: Harishankar
authors.affiliation: National Center for Laboratory Animal Sciences (ICMR), Jamai-Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Nappan V
authors.initials: NV
authors.lastname: Giridharan
authors.affiliation: Department of Lipid Biochemistry, National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, 500 007 Andhra Pradesh India.
authors.forename: Ayyalasomayajula
authors.initials: A
authors.lastname: Vajreswari
keywords: Adipose tissue; Apoptosis; Dietary supplementation; Nuclear receptors; Thermogenesis; Uncoupling protein; Vitamin A