A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

Abstract

Background/Aims: Altered nutrients during the in utero (IU) and/or lactation (L) period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD) fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT) mice were fed either a HFD or control chow (C) prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension) and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT₁- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.

Dietary habits, diversity, and predictors among pregnant women attending primary health care centers for antenatal care in Lagos, Nigeria

“…Studies have shown that an interaction between maternal high fat diet and the genotype during early life development can enhance the susceptibility to cardio-renal diseases later in life, hence potentiating the need to discourage or limit unhealthy snacking among pregnant women. [ 28 ]…”

Developmental origins of nonalcoholic fatty liver disease as a risk factor for exaggerated metabolic and cardiovascular-renal disease

“…Importantly, it is demonstrated by utilizing each of these models that there are overarching similarities by which IUGR offspring are predisposed to CVRD, which supports the developmental programming of chronic disease. IUGR offspring from many of these models have altered cardiomyocyte biology, including early reductions in cardiomyocyte numbers reported in offspring from dams with bilateral uterine ligation (30), decreased cardiomyocyte proliferation by postnatal day 1 in offspring of dams with maternal hypoxia (171), decreased cardiac expression of genes involved in heart's ability to produce energy from fatty acid oxidation in mice offspring exposed to maternal HFD by 27 wk of age (112), and increased contractile function of isolated left ventricles by 12 wk of age in offspring from nutrient-restricted dams (80). Moreover, data from these various models of developmental programming of CVRD in IUGR offspring show reductions in nephron endowment.…”

Effect of a Diet-Induced Obesity on the Progeny Response in a Murine Model

“…It has been reported that a high-fat diet, given during pregnancy and lactation in mice, could increase heart and kidney weight and reduce cardiac insulin responsiveness, expanding the risk of cardiorenal diseases in male mice [26]. However, our results showed the heart weight was more affected by the post-weaning diet (p = 8.84 × 10 −6 ) than the litter size (p = 0.009), not showing any significant effect of the maternal diet (p = 0.26).…”