Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice.
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).


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.
Isganaitis
Elvira
E
Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
Jimenez-Chillaron
Jose
J
Woo
Melissa
M
Chow
Alice
A
DeCoste
Jennifer
J
Vokes
Martha
M
Liu
Manway
M
Kasif
Simon
S
Zavacki
Ann-Marie
AM
Leshan
Rebecca L
RL
Myers
Martin G
MG
Patti
Mary-Elizabeth
ME
D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000254:growth & development; D000818:Animals; D001724:Birth Weight; D048429:Cell Size; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D006128:Growth / Q000502:physiology*; D006963:Hyperphagia / Q000453:epidemiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020644:Midline Thalamic Nuclei / Q000033:anatomy & histology / Q000254:growth & development; D011247:Pregnancy
D005947:Glucose