Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females.
Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice.
Departments of Molecular and Integrative Physiology and Internal Medicine (S.D.P., B.R.S., E.L.S., B.S.L., O.A.M.), and Division of Metabolism, Endocrinology and Diabetes (E.U.A., E.B.-M., O.A.M.), School of Medicine, University of Michigan, Ann Arbor, Michigan 48105; and Musculoskeletal Research (V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285.
Sebastian D
SD
Parlee
Becky R
BR
Simon
Erica L
EL
Scheller
Emilyn U
EU
Alejandro
Brian S
BS
Learman
Venkatesh
V
Krishnan
Ernesto
E
Bernal-Mizrachi
Ormond A
OA
MacDougald
D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D000831:Animals, Newborn; D000886:Anthropometry; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D064306:Non-Nutritive Sweeteners / Q000737:chemistry*; D012439:Saccharin / Q000737:chemistry*; D013739:Testosterone / Q000378:metabolism; D055114:X-Ray Microtomography
D007328:Insulin; D064306:Non-Nutritive Sweeteners; D013739:Testosterone; D012439:Saccharin