Chronic Tumor Necrosis Factor-α Infusion in Gravid C57BL6/J Mice Accelerates Adipose Tissue Development in Female Offspring

Objective:Tumor necrosis facto (TNF)-α is thought to mediate, in part, the link between obesity and insulin resistance, and women with gestational diabetes mellitus (GDM) have raised serum TNF-α concentrations. Our objective was to investigate whether systemic TNF-α administration into gravid C57BL6/J mice causes a GDM-like syndrome and affects growth and adipose tissue (AT) development in the offspring.Methods:We assessed glucose tolerance and reproductive outcome in mice infused with saline, or 2 μg or 4 μg recombinant mouse (rm)TNF-α by subcutaneous mini-osmotic pumps between days (d)11.5 and 18.5 of gestation. Subsequently, we studied the effects of the 2-μg dose on maternal AT metabolism. Finally, the growth of offspring exposed to 2 μg rmTNF-α in utero was followed until 8 weeks postnatal age. At 8 weeks, we assessed AT accumulation, as well as adipocyte area in white AT and insulin sensitivity in males, and adipokine mRNA levels in various AT depots in females.Results:The peak glucose response to a...