Chronic maternal vitamin B12 restriction induced changes in body composition & glucose metabolism in the Wistar rat offspring are partly correctable by rehabilitation

PLoS One. 2014 Nov 14;9(11):e112991. doi: 10.1371/journal.pone.0112991. eCollection 2014.

Abstract

Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers from conception or parturition and their offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with control males. Six each of pregnant B12R dams were rehabilitated from conception and parturition and their offspring weaned to control diet. While offspring of six B12R dams were weaned to control diet, those of the remaining six B12R dams continued on B12R diet. Biochemical parameters and body composition were determined in dams before mating and in male offspring at 3, 6, 9 and 12 months of their age. Dietary vitamin B12 restriction increased body weight but decreased LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams. Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%, basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12 months age, B12R offspring had higher (than controls) fasting plasma glucose, insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic enzyme activities were increased. B12R offspring had increased oxidative stress and decreased antioxidant status. Changes in body composition, glucose metabolism and stress were reversed by rehabilitating B12R dams from conception, whereas rehabilitation from parturition and weaning corrected them partially, highlighting the importance of vitamin B12 during pregnancy and lactation on growth, muscle development, glucose tolerance and metabolism in the offspring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / metabolism
  • Blood Glucose / analysis
  • Body Composition
  • Body Weight
  • Catalase / metabolism
  • Female
  • Glucose / metabolism*
  • Homocysteine / blood
  • Insulin / analysis
  • Liver / enzymology
  • Male
  • Malnutrition*
  • Maternal Nutritional Physiological Phenomena
  • Models, Animal
  • Oxidative Stress
  • Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Vitamin B 12 / blood*

Substances

  • Antioxidants
  • Blood Glucose
  • Insulin
  • Homocysteine
  • Catalase
  • Superoxide Dismutase
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Glucose
  • Vitamin B 12

Grants and funding

This work was supported by a research grant (# BT/PR-7506/PID/20/294/2006) to Manchala Raghunath, Giriraj Ratan Chandak and Shantanu Sengupta, from the Department of Biotechnology, Government of India, New Delhi, India (URL: http://dbtindia.nic.in/index.asp). The authors acknowledge the support and encouragement received from the Directors of National Institute of Nutrition and the Centre for Cellular and Molecular Biology, Hyderabad in the conduct of these studies. Kalle Anand Kumar is grateful to the Indian Council of Medical Research (ICMR), India, for awarding a senior research fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.