title: In uteroexposure to di-(2-ethylhexyl) phthalate induces metabolic disorder and increases fat accumulation in visceral depots of C57BL/6J mice offspring.
abstract: Excessive visceral fat accumulation is associated with metabolic disorders. Di-(2-ethylhexyl) phthalate (DEHP), a candidate environmental obesogen, affects lipid metabolism and adipogenesis. Perinatal exposure to DEHP may be associated with metabolic disorders of dams and offspring. The aim of the present study was to explore the effects of exposure of pregnant dams to DEHP on the metabolism and fat distribution of their offspring, and to determine the mechanisms for these effects. Pregnant C57BL/6J mice were administered DEHP via gavage (0.05 or 500 mg/kg/day) from gestational days 1-19. Pups were sacrificed at nine weeks of age. Serum leptin, insulin, lipid and fasting glucose levels, and the weights of the inguinal (subcutaneous) and gonadal (visceral) fat pads were determined. mRNA expression levels of two developmental genes, T-box 15 (Tbx15) and glypican 4 (Gpc4) were detected in fat tissues. A 100% abortion rate was exhibited in 500 mg/kg DEHP-treated dams, whereas exposure to 0.05 mg/kg DEHP did not affect reproductive outcomes. Pups from the 0.05 mg/kg exposure group were used for subsequent experimentation. Serum leptin, insulin, lipid and fasting glucose concentrations in these pups were significantly higher than those of control pups (P<0.05). Although no significant change in body weight was detected, the visceral fat weights of DEHP-exposed pups were significantly higher than those of control pups (P<0.05). Compared with controls, mRNA expression levels ofTbx15in subcutaneous fat andGpc4in visceral fat were significantly increased among DEHP-exposed pups (P<0.01). The present results suggest thatin uteroexposure to an environmentally safe dose of DEHP may lead to excessive visceral fat accumulation and metabolic disorders in offspring and that aberrant expression ofTbx15andGpc4may have an important role in these effects.
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Hailun
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Medical Laboratory Testing, Liaoning Medical Vocational College, Shenyang, Liaoning 110101, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ding
authors.affiliation: Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
keywords: T-box 15; di-(2-ethylhexyl) phthalate; fat distribution; glypican 4; visceral fat