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

doi:10.2337/db08-1266

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

¹Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts; the
²Hospital Sant Joan de Deu, Universitat de Barcelona, Barcelona, Spain; the
³Department of Biomedical Engineering, Boston University, Boston, Massachusetts; the
⁴Center for Advanced Genomic Technology, Boston University, Boston, Massachusetts; the
⁵Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and the
⁶Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.

Corresponding author: Mary-Elizabeth Patti, mary.elizabeth.patti{at}joslin.harvard.edu.

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, AccI, 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.

Footnotes

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See accompanying commentary, p. 1037.
- Received September 12, 2008.
- Accepted February 4, 2009.
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