Maternal obesity impairs heart health and function of the fetus according to a new study mouse study published in The Journal of Physiology. The study found that maternal obesity causes molecular changes in the heart of the fetus and alters expression of genes related to nutrient metabolism, which greatly increases offspring’s risk of cardiac problems in later life.
The authors point out that the global prevalence of obesity in in women of reproductive age is continuing to increase at a rapid pace and that children born to women with obesity during pregnancy are at a 30% greater risk for cardiovascular disease in adulthood. This study shows that the heart is ‘programmed’ by the nutrients it receives in fetal life. Changes in the expression of genes alter how the heart normally metabolizes carbohydrates and fats. They shift the heart’s nutrient preference further toward fat and away from sugar. As a result, the hearts of fetuses of obese female mice were larger, weighed more, had thicker walls, and showed signs of inflammation. This impairs how efficiently the heart contracts and pumps blood around the body.
Researchers from University of Colorado used a mouse model that replicates human maternal physiology and placental nutrient transport in obese women. Female mice (n=31) were fed a diet with a high fat content together with a sugary drink, which is equivalent to a human regularly consuming a burger, chips, and a fizzy drink (1500kcal). The female mice ate this diet until they developed obesity, putting on about 25% of their original body weight. 50 female mice were fed a control diet.
Mouse pups (n=187) were studied in utero, as well as after birth at 3, 6, 9 and 24 months using imaging techniques, including echocardiography and positron emission tomography (PET) scans. Researchers analyzed genes, proteins, and mitochondria of the offspring.
The changes in offspring cardiac metabolism strongly depended on sex. The expression of 841 genes were altered in the hearts of female fetuses and 764 genes were altered in male fetuses, but less than 10% genes were commonly altered in both sexes. Interestingly, although both male and female offspring from mothers with obesity had impaired cardiac function, there were differences in the progression between sexes; males were impaired from the start, whereas females’ cardiac function got progressively worse with age.
The sex-difference in the lasting impairments of cardiovascular health and function could be due to estrogen. Higher levels in young females may protect cardiovascular health, the protection diminishes as estrogen levels deplete as the females age. The molecular cause for the sex difference is not yet understood.
Mice have shorter pregnancies, more offspring, and different diets to humans so further studies in human volunteers would be required to extrapolate the findings to women’s health. Loss-of-function studies also need to be carried out to prove this mechanism linking maternal obesity and offspring heart function and pinpoint the exact molecules responsible.