Abstract
Obesity and noncommunicable diseases (NCDs) like diabetes are epidemic in India. Developmental
origins of health and disease hypothesis, based on epidemiological evidence, associates
maternal undernutrition and low birth weight (LBW) of the offspring with increased
obesity and diabetes in their later life. Considering widespread maternal micronutrient
(MN) deficiencies, LBW, and NCDs in India, we tested the hypothesis, “maternal MN
deficiency per se programs the offspring for obesity and increases risk for NCDs in
their later life” in rodent models. We showed in Wistar rat offspring that maternal
MN (single or combined) deficiency per se: (1) increased body fat (visceral fat) and
altered lipid metabolism, (2) decreased lean body and fat free mass, and (3) altered
muscle function and altered glucose tolerance/metabolism and insulin sensitivity.
Rehabilitation prevented vitamin but not mineral restriction-induced changes in offspring,
which showed partial mitigation. Increased oxidative/steroid stress, decreased antioxidant
status, and inflammatory state were the associated common mechanisms in the offspring.
Our attempts to assess the role of epigenetics showed that folate and/or vitamin B12
deficiencies altered mother’s body composition besides that of the offspring. Additionally,
in C57BL/6 mice, B12 deficiency-induced anxiety was observed in mothers and offspring.
That expressions of histone modifying enzymes in mice brain and promoter methylation
of adiponectin, leptin, and 11βHSD1 genes in rat offspring were altered in MN (B12 and Mg) deficiency suggested that
altered epigenetics most likely plays a role in maternal MN deficiency-induced changes
in body fat/lipid metabolism and anxiety-like behavior in mothers and offspring.
Keywords
micronutrient restriction - body composition - insulin resistance - lipid and carbohydrate
metabolism - oxidative stress - epigenetics
