title: Adipose tissue in offspring of Lepr(db/+) mice: early-life environment vs. genotype.
abstract: Gravidas with obesity and diabetes ("diabesity") may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr(db/+) 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 factor-alpha expression 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.
authors.affiliation: Experimental Obstetrics and Gynecology, Onderwijs en Navorsing, Campus Gasthuisberg box 611, Herestraat 49, 3000 Leuven, Belgium. suzan.lambin@med.kuleuven.be
authors.forename: Suzan
authors.initials: S
authors.lastname: Lambin
authors.forename: Rita
authors.initials: R
authors.lastname: van Bree
authors.forename: Silvia
authors.initials: S
authors.lastname: Caluwaerts
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Vercruysse
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Johan
authors.initials: J
authors.lastname: Verhaeghe
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001835:Body Weight; D003433:Crosses, Genetic; D048909:Diabetes Complications / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D015430:Weight Gain
chemical_list: D011956:Receptors, Cell Surface; D054411:Receptors, Leptin