Effects of Neonatal Saccharin Exposure on Body Composition and Glucose Metabolism of Adult Mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 702-709-Obesity: Response to Interventions
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-705
Sebastian D Parlee*1, Becky R Simon1, Erica L Scheller1, Emilyn U Alejandro2, Brian S Learman1, Venkatesh Gary Krishnan3, Ernesto Bernal-Mizrachi1 and Ormond A MacDougald1
1University of Michigan, Ann Arbor, MI, 2Univ of Michigan, Ann Arbor, MI, 3Eli Lilly and Company, Indianapolis, IN
During perinatal and neonatal development, mammals are susceptible to nutritional and pharmacological perturbations, which can have persistent effects on development and function of white adipose tissue (WAT), and can alter susceptibility to obesity later in life. Our laboratory found that the heterodimeric sweet taste receptors, T1R2 and T1R3, are expressed in preadipocytes and throughout adipogenesis. Stimulation of preadipocyte T1R2/T1R3 with synthetic sweet agonists (e.g. saccharin) promotes adipogenesis whereas stimulation of adipocyte T1R2/T1R3 inhibits basal and forskolin-induced lipolysis. Conversely, knockdown of T1R3 inhibits adipogenesis under standard culture conditions. We propose that preadipocytes and adipocytes use T1R2/T1R3 to sense increases in dietary or cellular metabolites to stimulate adipogenesis and decrease lipolysis in an effort to store excess energy, alleviating metabolic stress and T2D.  To identify whether neonatal exposure to saccharin affects early developmental adipogenesis, C56BL/6J neonates were exposed to saccharin via maternal lactation from birth until weaning. Serum concentrations of saccharin averaged ~280 mM in p5 pups. Following 13 weeks on western diet, the body weight of male or female mice exposed to saccharin as neonates did not differ to that of control mice. Saccharin exposure did, however, significantly decrease fat mass and increase lean and trabecular bone mass in male mice, without affecting food intake. Decreased total body fat by NMR corresponded to decreased mass of epididymal, perirenal and subcutaneous WAT depots. Reduced weight of epididymal WAT following saccharin treatment was due to increased frequency of smaller adipocytes and reduced number of large adipocytes, without a change in total adipocyte number. Mice exposed to saccharin showed improved glucose tolerance without changes to insulin secretion. These results demonstrate that neonatal saccharin exposure alters body composition and metabolic health in adult mice.

Nothing to Disclose: SDP, BRS, ELS, EUA, BSL, VGK, EB, OAM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by grants from the National Institutes of Health (RO1 DK95705 to O.A.M, RO1 DK073716 & RO1 DK084236 to E.M, 2T32DK071212-06 to E.U.A); S.D.P and B.R.S were supported by training grants from the University of Michigan Training Program in Organogenesis (T32-HD007505). B.R.S. was also supported by the CMB training grant (T32-MG007315) and a Rackham Merit Fellowship.