MICROMouse Program Application Abstract
Increased risk for diabetes and obesity in offspring of multiparous mice.
Laura Woollett (Cincinnati, OH)
Infants exposed to more fat or glucose in utero are at an increased risk to develop diabetes and/or obesity later in life in both humans and rodents. From our previous MicroMouse proposal, we have shown that adult offspring of female mice in their fourth pregnancy are at an increased risk to become obese and have altered glucose excursion as compared to adult offspring of female mice in their first pregnancy. Part of the reason for the changes is that females from multiple pregnancies have more fat (C57BL/6 and FVB/N) and abnormal glucose tolerance tests (C57BL/6). Interestingly, the increased adiposity was not due to an older aged C57BL/6 dam, but to number of pregnancies, unlike FVB/N dams in which adiposity was similar in age-matched dams, regardless of number of previous pregnancies. In this competitive renewal, we hypothesize the adult offspring from the fourth pregnancies will have altered metabolism that promote lipid accretion in the adipose tissues, possibly due to changes in expression levels of key metabolic regulators, such as PPAR?. We also hypothesize that pregnancy alone will convert adipose tissue to an anabolic tissue that will accrue lipid, at least in the C57BL/6 dams, similar to that which occurs in humans. Thus, the aim of this proposal is to determine the mechanism responsible for the altered lipid and glucose metabolism in adult offspring of dams in their fourth vs first pregnancies. We will also begin to dissect the mechanism responsible for lipid accretion in multiparous C57BL/6 dams. These studies are important for two reasons. First, most mouse colonies are maintained by breeder mice that are bred multiple times, which could be a major confounding factor of studies intended to examine a specific intervention in the development of obesity and diabetes. Delineating the mechanism responsible for the altered metabolism will help researchers delineate the known intervention vs that confounded by breeding methods. Second, we are currently in an obesity epidemic which could be fueled by adult offspring of obese/diabetic mothers becoming obese, having offspring with an increased risk for obesity as adults, etc. We have generated a unique model of overabundant in utero nutrition in the mouse that can be used to help glean the role of fetal programming in the obesity epidemic.
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