Moderate caloric restriction in lactating rats protects offspring against obesity and insulin resistance in later life

Abstract

We aimed to assess the lasting effects of caloric restriction in lactating rats on body weight and insulin sensitivity of their offspring. Dams were fed with either ad libitum standard diet or a 30% caloric restricted diet throughout lactation. After weaning, the offspringwerefed with a normal-fat diet until the age of 15 wk, and then with a normal- or a high-fat (HF) diet until the age of 26 wk. Blood parameters were measured during ad libitum feeding conditions and after 14-h fasting. Food preferences were also measured. In dams, milk leptin concentration and leptinmRNAand protein levels in mammary gland were also determined. Caloric restricted dams showed higher mRNA and protein levels of leptin in mammary gland than controls, without significant changes in milk leptin concentration. The offspring of caloric restricted dams (CR) ate fewer calories and showed lower body weight gain and fat accumulation under the HF diet than their controls. CR also maintained unchanged circulating leptin levels under HF diet, whereas levels increased in controls. In addition, male CR were resistant to the increase of circulating triglyceridesandof the homeostaticmodelassessment for insulin resistance produced in male controls under HF diet feeding; CR were also protected against the increased preference for fat-food occurring in females upon HF diet. These results suggest moderate caloric restrictionduringlactation protectsfromobesitydevelopmentin offspring inadultlifeandfrom the related metabolic alterations, particularly dyslipidemia, insulin resistance, and hyperleptinemia, associated with HF diet feeding. (Endocrinology 151: 1030-1041, 2010) Copyright © 2010 by The Endocrine Society.