Accelerated Postnatal Growth Increases Lipogenic Gene Expression and Adipocyte Size in Low–Birth Weight Mice

Abstract

OBJECTIVE To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS ICR mice were food restricted by 50% from gestational days 12.5–18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured. RESULTS At age 3 weeks, LBW mice with CUG (designated U-C) had body weight comparable with controls (designated C-C); weight was reduced by 49% in LBW mice without CUG (designated U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U mice ( P < 0.05 vs. C-C mice). Adipose expression of the lipogenic genes Fasn , Acc I, Lpin1 , and Srebf1 was significantly increased in U-C compared with both C-C and U-U mice ( P < 0.05). Mitochondrial DNA copy number was reduced by >50% in U-C versus U-U mice ( P = 0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U mice ( P < 0.01). CONCLUSIONS CUG results in increased adipose tissue lipogenic gene expression and adipocyte diameter but not increased cellularity, suggesting that catch-up fat is primarily associated with lipogenesis rather than adipogenesis in this murine model.

Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice

“…The difference between the two diets may affect fat storage in the mothers and modify fat content in the milk during suckling. In fact, the catch-up growth in the other model has been recently shown to be associated with increased gonadal fat, lipogenic gene expression and adipocyte size [20], whereas our adult animals showed decreased adiposity. Alternatively, the differences observed between the two models may also arise from the duration of food restriction, which in our model starts 1 day earlier [19].…”

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

“…The studies to date have reported increased fat accumulation after catch-up growth in low birthweight infants and in animal models of IUGR [30,31] . Previous studies in rats have demonstrated that the majority of body fat is located in subcutaneous deposits at the time of weaning (subcutaneous fat weight increases 6-fold).…”

Inflammatory links between obesity and metabolic disease

“…Placental inflammation is a characteristic of maternal obesity, a risk factor for obesity in offspring, and involves inflammatory macrophage infiltration that can alter the maternal-fetal circulation (74). Inflammatory disturbances in the placenta may alter the nutrient set points established early in life and predispose to an accelerated pattern of catch-up growth that contributes to the risk for later obesity, especially in low-birth-weight infants (75,76). The concept that inflammatory networks can influence the predilection toward obesity is supported by the find-ings that variation in obesity susceptibility between mouse strains is intrinsically linked to the inflammatory networks and leukocyte composition of adipose tissue established prior to HFD exposure (77).…”