Adult‐onset obesity induced by early life overnutrition could be reversed by caloric restriction

Abstract

Overnutrition during the suckling period (small litter, SL) results in the development of adult‐onset obesity. The aim of the study was to investigate if caloric restriction (CR) in the postweaning period can reverse this phenomenon. The control litter (CL) had 12 pups/dam and SL had 3 male pups/dam from the postnatal day 3 until 21. In the postweaning period rats consumed lab chow as indicated: (i) CL and SL groups were on ad libitum regimen up to day 140, (ii) SL/CR group received 24% reduction in daily food intake compared to SL, and (iii) SL/CR/AL group was on 24% CR up to day 94 and then switched over to ad libitum feeding. CR caused reduction in body weight gains and normalized serum glucose, insulin, and leptin levels in SL/CR and SL/CR/AL rats compared to CL. The expression of neuropeptide Y (Npy) and leptin receptor (Lepr) returned to control levels in the hypothalami from SL/CR and SL/CR/AL rats compared to CL. No differences in the expression of pro‐opiomelanocortin and insulin receptor (Insr) were observed among these groups. Altered methylation of specific CpG dinucleotides in the proximal promoter region was observed for the Npy and Insr among these groups. CR resulted in normalized metabolic phenotype and gene expression involved in controlling food intake. The results show that the CR can be a successful intervention for reversing obese phenotype induced by lactational overfeeding.Grant Funding Source: NIH DK61518