AJOG Reviews
Diet-induced obesity in the rat: A model for gestational diabetes mellitus

https://doi.org/10.1016/j.ajog.2003.09.025Get rights and content

Abstract

Objectives

Obesity is one of the most important risk factors for the development of gestational diabetes mellitus (GDM). However, in obese women, it is difficult to disentangle the genetic and environmental contributions. The aim of this study was to investigate whether diet-induced obesity results in GDM in rats with the same genetic background.

Study design

Female Wistar rats were fed a cafeteria-style diet (CAF) or the standard control (C) diet from 70 days of age onward. After 4 weeks on the diets, subgroups of CAF and C rats were mated. In virgin and late-pregnant CAF and C rats, we determined body weight, body composition by dual-energy x-ray absorptiometry (DEXA), glucose tolerance by intravenous glucose tolerance test (IVGTT), and insulin sensitivity by hyperinsulinemic euglycemic clamp in nonanesthesized rats. Plasma leptin concentrations were also measured.

Results

Body weight increased after 4 weeks in virgin CAF rats (P<.0001) and exceeded that of C rats throughout pregnancy. This resulted exclusively from increased fat mass, as determined by DEXA, and was associated with a rise in plasma leptin concentrations in nonpregnant and pregnant (both P<.0001) CAF rats. During the IVGTT, nonpregnant CAF rats showed normal glucose levels but increased insulin levels compared with C rats (P<.05 for the area under the curve for insulin: AUCinsulin). In pregnant CAF animals, glucose tolerance was clearly impaired (AUCglucose: P<.001) with insulin also raised (AUCinsulin: P<.05). On day 22, fetal weight was comparable between C and CAF rats, but litter weight was higher in CAF rats (P<.05) owing to an increase in litter size. Hyperinsulinemic clamp studies revealed unequivocal insulin resistance in nonpregnant CAF rats, which was aggravated by pregnancy, the proportional effect of obesity being higher than that of pregnancy.

Conclusion

Diet-induced obesity in rats is associated with glucose intolerance during pregnancy but not in the nonpregnant state. This is likely to result from the additive effects of obesity and pregnancy on insulin sensitivity. This obese rat model is an attractive model to study further the physiologic and molecular abnormalities in GDM.

Section snippets

Material and methods

The entire protocol was reviewed and approved by the local Ethical Committee for Animal Procedures (Katholieke Universiteit Leuven, Belgium).

Body weights and determination of parameters in blood (Table I and II)

After 4 weeks on either diet, CAF rats weighed significantly more than C rats (278.1±1.7 in CAF rats vs 250.8±1.3 in C rats, P<.0001). Four weeks on the cafeteria diet increased the rats' body weight by 31% compared with 16% for rats on the standard laboratory chow (Figure 1). Furthermore plasma glucose levels as well as plasma insulin and leptin concentrations were significantly increased in CAF rats (P<.01, P<.001, and P<.001, respectively; Table I). During pregnancy, CAF rats gained more

Comment

Gestational diabetes was achieved in this study by feeding pregnant rats a high-calorie “cafeteria” diet. This novel method of GDM development in rodents provides a very attractive model for the study of GDM, attractive because of its simplicity and because of its resemblance to GDM in women. It is associated with, and is likely to be initiated by, the most important risk factor for GDM in women (ie, obesity), an increasingly prevalent metabolic disorder of energy imbalance. The recent increase

References (30)

  • B.D Wilson et al.

    The role of agouti-related protein in regulating body-weight

    Mol Med Today

    (1999)
  • A.H Mokdad et al.

    Diabetes trends in the US: 1990-1998

    Diabetes Care

    (2000)
  • P Passa

    Diabetes trends in Europe

    Diabetes Metab Res Rev

    (2002)
  • I Campbell

    The obesity epidemic: can we turn the tide?

    Heart

    (2003)
  • Tackling obesity in England

    (2001)
  • K.G.M.M Alberti et al.

    Definition, diagnosis and classification of diabetes mellitus and its complications, 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation

    Diabetic Med

    (1998)
  • C.G Solomon et al.

    A prospective study of pregravid determinants of gestational diabetes mellitus

    JAMA

    (1997)
  • S Bo et al.

    Dietary fat and gestational hyperglycaemia

    Diabetologia

    (2001)
  • S Ellard et al.

    A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria

    Diabetologia

    (2000)
  • P.M Catalano et al.

    Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus

    J Nutr

    (2003)
  • C.J Petry et al.

    Early protein restriction and obesity independently induce hypertension in 1-year-old rats

    Clin Sci

    (1997)
  • K Holemans et al.

    Insulin sensitivity in adult female offspring of rats subjected to malnutrition during the perinatal period

    J Soc Gynecol Investig

    (1996)
  • J Damas et al.

    Insulin sensitivity, clearance and release in kininogen-deficient rats

    Exp Physiol

    (1999)
  • P.S Widdowson

    Obesity in diabetes and the impact of leptin

    Diabetes Rev Int

    (1997)
  • S Caluwaerts et al.

    Is low-dose streptozotocin in rats an adequate model for gestational diabetes mellitus?

    J Soc Gynecol Investig

    (2003)
  • Cited by (0)

    Supported by VIS grant No. VIS/00/008 from the Katholieke Universiteit Leuven, Belgium.

    View full text