Editors' ChoiceFetal Metabolic Programming

Mom's Diet and Baby's Appetite

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Science Translational Medicine  07 Apr 2010:
Vol. 2, Issue 26, pp. 26ec54
DOI: 10.1126/scitranslmed.3001122

The “Barker hypothesis” suggests that adult disease is influenced by conditions during early development; obesity, for example, has been linked to fetal conditions in the intrauterine environment. Body weight homeostasis and energy balance are regulated in large part by the melanocortin system—a group of receptors and their endogenous agonists and inverse agonists—of the hypothalamus. However, how maternal diet affects the development of this system in the fetus is unknown.

Now, Grayson et al. show that compared with monkey fetuses from mothers fed a control diet (13% of calories from fat), monkey fetuses from mothers fed a high-fat diet (35% of calories from fat) have alterations in the expression of both proopiomelanocortin, the precursor of α-melanocyte stimulating hormone (a potent “anorexic” peptide that decreases food intake and is the major agonist of the melanocortin system), as well as agouti-related peptide, a strong appetite stimulant and inverse agonist of the melanocortin system. Both the mothers and fetuses exposed to the high-fat diet had elevated levels of cortisol, and hypothalamic tissue from these fetuses showed increased expression of proinflammatory cytokines, which might further alter the development of the melanocortin system and cause postnatal dysregulation of energy balance. Importantly, these developmental abnormalities in the fetus could be prevented by switching the mothers from the high-fat diet to the regular control diet before a future pregnancy.

Given the similarities between nonhuman primate and human physiology, the high-fat nature of the typical Western diet, and the fact that greater than 50% of women of childbearing age are either overweight or obese in the United States, these findings are applicable to human health and reinforce the importance of the maternal diet and the in utero environment on fetal metabolic programming.

B. E. Grayson et al., Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology 151, 1622–1632 (2010). [Abstract]

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