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in obese women with
gestational diabetes: relationship to FFA during pregnancy
Departments of 1 Reproductive Biology and 2 Nutrition, Case Western Reserve University School of Medicine, and MetroHealth Medical Center, Cleveland, Ohio 44106; and 3 Department of Nutrition, Texas A & M University, College Station, Texas 77843
Gestational diabetes
mellitus (GDM) is associated with elevated postprandial free fatty
acids (FFA) and insulin resistance; however, little is known about the
cellular mechanisms underlying insulin resistance to suppress lipolysis
during gestation. We evaluated the longitudinal changes in insulin
suppression of FFA before pregnancy and in early (12-14 wk) and
late (34-36 wk) gestation in obese subjects with normal glucose
tolerance and in obese GDM subjects. Abdominal subcutaneous adipose
tissue biopsies were also obtained during cesarean delivery from normal
obese pregnant (Preg-Con), GDM, and nonpregnant obese control
(Non-Preg-Con) subjects during gynecological surgery. GDM subjects had
higher basal plasma FFA before pregnancy (P = 0.055).
Insulin's ability to suppress FFA levels declined from early to late
gestation in both GDM and Preg-Con subjects and was significantly less
in GDM subjects compared with Preg-Con subjects over time
(P = 0.025). Adipose tissue insulin receptor substrate
(IRS)-1 protein levels were 43% lower (P = 0.02) and
p85
subunit of phosphatidylinositol 3-kinase was twofold higher
(P = 0.03) in GDM compared with Preg-Con subjects. The
levels of peroxisome proliferator-activated receptor-
(PPAR
) mRNA
and protein were lower by 38% in Preg-Con (P = 0.006) and by 48% in GDM subjects (P = 0.005) compared with
Non-Preg controls. Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects (P < 0.002). Thus GDM women have decreased
IRS-1, which may contribute to reduced insulin suppression of lipolysis
with advancing gestation. Decreased PPAR
and its target genes may be
part of the molecular mechanism to accelerate fat catabolism to meet
fetal nutrient demand in late gestation.
insulin signaling; lipid metabolism; body weight; adipogenesis
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