title: Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring.
abstract: Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation. Offspring were fed on control diet post-weaning and studied till 30 weeks. Lipid profile, serum glutamate pyruvate transaminase (SGPT), calcium and vitamin D levels were analyzed. Liver fat deposition, omega-3 fatty acids level and mRNA expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), interleukin 6 (IL-6), superoxide dismutase 1 (SOD-1) and uncoupling protein 2 (UCP2) were determined. Low serum vitamin D levels with an increase in SGPT and TG levels in CaD and VDD female offspring were observed. Severe liver steatosis with down-regulation of PPAR-α and UCP2 and up-regulation of SREBP-1c, IL-6 and SOD-1 was observed in the female offspring born to deficient dams. CaD and VDD male offspring showed mild steatosis and down-regulation of UCP2 and SOD-1. We conclude that maternal calcium and vitamin D deficiency programs abnormal lipid metabolism and hepatic gene expression in the F1 generation female offspring leading to hepatic steatosis, despite feeding them on control diet post-weaning.
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, Pune 411004, Maharashtra, India.
authors.forename: Sona S
authors.initials: SS
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Nivedita M
authors.initials: NM
authors.lastname: Jangale
authors.affiliation: Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Abhay M
authors.initials: AM
authors.lastname: Harsulkar
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, Pune 411004, Maharashtra, India.
authors.forename: Medha K
authors.initials: MK
authors.lastname: Gokhale
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, Pune 411004, Maharashtra, India. Electronic address: bnjoshiari@gmail.com.
authors.forename: Bimba N
authors.initials: BN
authors.lastname: Joshi
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000097:blood / Q000172:deficiency*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006505:Hepatitis / Q000209:etiology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000502:physiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D017208:Rats, Wistar; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000235:genetics*
chemical_list: D015525:Fatty Acids, Omega-3; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000410:Alanine Transaminase; D002118:Calcium
keywords: Calcium; Genes; Hepatic steatosis; Vitamin D; Wistar rats