Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

Abstract

Background/objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance.

Subjects/methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue.

Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001).

Conclusions: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Figure 1

Adipose tissue sections (a–c) and isolated adipocytes (d) from a NW pregnant woman in T1. The sections were stained with antibodies against mast cell tryptase to detect mast cells (a), CD68 to detect macrophages (b) and von Willebrand factor to visualize vessels (c). Warp Red was used as the chromogen. Slides were counterstained with hematoxylin. Arrows indicate positive immunoreactions. Scale bar represents 50 μm.

Figure 2

Correlation between adipocyte diameter in T1 and change in the proportion of adipocytes <100 μm in diameter during pregnancy in NW and obese women (ρ=0.616, P<0.001, n=33).