Accelerated Postnatal Growth Increases Lipogenic Gene Expression and Adipocyte Size in LBW 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 to 18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad lib, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were sacrificed at age 3 weeks and gonadal fat 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 to controls (C-C); weight was reduced by 49% in LBW mice without CUG (U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U (p<0.05 vs. C-C). Adipose expression of the lipogenic genes Fasn, Acc1, Lpin1, and Srebf1 was significantly increased in U-C as compared to both C-C and U-U (p<0.05). Mitochondrial DNA copy number was reduced by >50% in U-C vs. U-U (p=0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U (p<0.01).

Conclusions: Catch-up growth 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.