Accretion of visceral fat and hepatic insulin resistance in pregnant rats.
Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF-; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 +/- 0.3, Preg 10.0 +/- 1.0 g, P < 0.01), and PVF- had similar amounts of VF compared with Nonpreg (PVF- 4.6 +/- 0.8 g). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg.kg(-1).min(-1)) was highest in Nonpreg (19.4 +/- 2.0), lowest in Preg (11.1 +/- 1.4), and intermediate in PVF- (14.7 +/- 0.6; P < 0.001 between all groups). During the clamp, Nonpreg had greater hepatic insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 +/- 1.3, Preg 9.3 +/- 0.5 mg.kg(-1).min(-1); P < 0.001]. With decreased VF, hepatic insulin sensitivity was similar to nonpregnant levels in PVF- (HGP 4.9 +/- 0.8 mg.kg(-1).min(-1)). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 +/- 0.4 vs. Preg 3.2 +/- 0.3 mg/g) and decreased with removal of VF (PVF- 1.3 +/- 0.4 mg/g; P < 0.05). Accretion of visceral fat is an important component in the development of hepatic IR in pregnancy, and accumulation of hepatic triglycerides is a mechanism by which visceral fat may modulate insulin action in pregnancy.
Einstein
Francine H
FH
Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology and Women's Health, The Albert Einstein College of Medicine/Montefiore Medical Center, 1825 Eastchester Road, Bronx, NY 10461, USA. feinstei@montefiore.org
Fishman
Sigal
S
Muzumdar
Radhika H
RH
Yang
Xiao Man
XM
Atzmon
Gil
G
Barzilai
Nir
N
D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001823:Body Composition / Q000502:physiology; D002404:Catheterization; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D036361:Peptide Hormones / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D054392:Adipokines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D036361:Peptide Hormones; D014280:Triglycerides; D012313:RNA