Adipose tissue in offspring of Lepr mice: early-life environment vs. genotype

Lambin S, van Bree R, Caluwaerts S, Vercruysse L, Vergote I, Verhaeghe J. Adipose tissue in offspring of Lepr db/ mice: early-life environment vs. genotype. Am J Physiol Endocrinol Metab 292: E262–E271, 2007. First published September 5, 2006; doi:10.1152/ajpendo.00308.2006.—Gravidas with obesity and diabetes (“diabesity”) may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr diabese mouse to examine the magnitude of these transmission modes, focusing on adipose tissue (AT). We compared the following six groups: wild-type ( / ) offspring from / or db/ dams (different early life environment) and db/ offspring from db/ dams, fed a standard or high-fat diet. Weight gain (0–8 wk) was higher in / offspring from db/ vs. / mothers, and even higher in db/ vs. / offspring from db/ mothers. In addition, we observed a stepwise increase in AT and adipocyte size in / from / mice, / from db/ mice, and db/ mice at 8 wk. Differences in weight and adiposity between / offspring from db/ vs. / dams were more pronounced in males than in females. Leptin and apelin mRNA levels in white and brown AT were higher in / offspring from db/ vs. / dams; however, leptin, apelin, and tumor necrosis factorexpression were boosted more robustly in db/ offspring. The high-fat diet amplified AT differences between db/ vs. / offspring from db/ dams, but not between / offspring from db/ vs. / dams. Moreover, db/ but not / offspring from db/ mothers were insulin-resistant and hyperinsulinemic after a glucose challenge. In conclusion, the genetic transmission of the diabesity phenotype clearly prevailed, but the early-life diabesity environment had discernible effects on postnatal weight gain as well as on adipocyte size and adipokine expression at a postpubertal age.