Ingestion of Carbohydrate-Rich Supplements during Gestation Programs Insulin and Leptin Resistance but not Body Weight Gain in Adult Rat Offspring

Abstract

Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important modifications in hormonal status is a period of changes in normal feeding habits with pulses of consumption or avoidance of certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their daily intake with either a restricted control (Cr), high-fat (HF), or high-carbohydrate (HC) diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca) served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin) were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females (-16%; p < 0.001) and their offspring presented a weight deficit from birth until 6 (HC group) and 10 (Cr group) weeks of age (p < 0.05 or less). Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose, and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%; p < 0.001), but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC, and HF offspring (+33-100% vs Ca; p < 0.05 or less). HC supplement ingestion during gestation therefore leads to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest that attention should be paid to the carbohydrate snacking and overall carbohydrate content in the diet during the last weeks (or months) preceding delivery to limit development of later metabolic disorders in offspring.

Keywords: adipose tissue distribution; dietary preference; fetal programming; ghrelin; high-fat; hypothalamic Ob-Rb expression.

Figure 1

Schematic representation of the experimental protocol.

Figure 2

Energy intake [(A); mean ± SEM in kcal/day) before, and during the first (day 1 to day 12) and second part (day 12 to day 21) of gestation (A), proportional increase in energy intake during the second part of gestation vs before gestation (B), and body weight gain (mean ± SEM in% vs before gestation) (C) in dams fed during gestation either a control diet (Ca group; n = 11) ad libitum, or a restricted control (Cr group; n = 15), a high-fat (HF group; n = 10) or a high-carbohydrate (HC group; n = 10) diet ad libitum for 6 h during the light period, in addition to two normal meals given during the dark period. *p < 0.05, **p < 0.01 and ***p < 0.001 vs Ca; ^##p < 0.01 and ^###p < 0.001 vs HF.

Figure 3

Postnatal (PN) body weight (mean ± SEM in grams) at different times of the suckling period [PN days 1–21; (A)] and after weaning (B) at PN weeks 6, 10, and 20 in offspring from dams fed during gestation either a control diet (Ca group) ad libitum, or a restricted control (Cr group), a high-fat (HF group) or a high-carbohydrate (HC group) diet ad libitum for 6 h during the light period, in addition to two normal meals given during the dark period. *p < 0.05, **p < 0.01, and ***p < 0.001 vs Ca; ^#p < 0.05 and ^##p < 0.01 vs HF; ⁺p < 0.05 vs HC.

Figure 4

Intakes (mean ± SEM in grams) of high-fat (HFS) and high-carbohydrate (HCS) isocaloric solutions during dietary preference tests performed during light (A) and dark (B) periods in offspring from dams fed during gestation either a control diet (Ca group) ad libitum, or a restricted control (Cr group), a high-fat (HF group) or a high-carbohydrate (HC group) diet ad libitum for 6 h during the light period, in addition to two normal meals given during the dark period. ^≠p < 0.001 between HF and HC intakes for the same group; **p < 0.01, and ***p < 0.001 vs Ca; ^#p < 0.05 vs HF; ⁺⁺p < 0.01 vs HC.

Figure 5

Plasma concentrations of leptin [mean ± SEM in ng/mL; (A)] and mRNA expression of the long form of leptin receptor (Ob-Rb) in the arcuate (ARC) nucleus of the hypothalamus (B) in adult offspring from dams fed during gestation either a control diet (Ca group) ad libitum, or a restricted control (Cr group), a high-fat (HF group) or a high-carbohydrate (HC group) diet ad libitum for 6 h during the light period, in addition to two normal meals given during the dark period. *p < 0.05, and **p < 0.01 vs Ca; ^###p < 0.001 vs HF; ⁺p < 0.05 vs HC; ^§p < 0.05 and ^§§§p < 0.001 vs Cr.

Figure 6

Correlations between fat depot weights and leptin (A,B), fat depot weight and hypothalamic leptin receptor (Ob-Rb) expression (C), and Ob-Rb expression and leptin (D) in adult offspring from dams fed during gestation either a control diet ad libitum, or a control, a high-fat, or a high-carbohydrate diet ad libitum for 6 h during the light period, in addition to two normal meals given during the dark period. AU: arbitrary unit; SC: subcutaneous.