Programming of Mouse Obesity by Maternal Exposure to Concentrated Ambient Fine Particles

Part Fibre Toxicol. 2017 Jun 23;14(1):20. doi: 10.1186/s12989-017-0201-9.

Abstract

Background: Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM2.5) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated.

Results: To determine if maternal exposure to PM2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pre-conception, pregnancy, and lactation, and the developmental and metabolic responses of offspring were assessed. The growth trajectory of offspring revealed that maternal exposure to CAP significantly decreased offspring birth weight but increased body weight of adult male but not female offspring, and the latter was expressed as increased adiposity. These adult male offspring had increased food intake, but were sensitive to exogenous leptin. Their hypothalamic expression of Socs3 and Pomc, two target genes of leptin, was not changed, and the hypothalamic expression of NPY, an orexigenic peptide that is inhibited by leptin, was significantly increased. These decreases in central anorexigenic signaling were accompanied by reduced plasma leptin and its expression in adipose tissues, the primary source of circulating leptin. In contrast, maternal exposure did not significantly change any of these indexes in adult female offspring. Pyrosequencing demonstrated that the leptin promoter methylation of adipocytes was significantly increased in CAP-exposed male but not female offspring.

Conclusions: Our data indicate that maternal exposure to ambient PM2.5 programs obesity in male offspring probably through alterations in the methylation of the promoter region of the leptin gene.

Keywords: DNA methylation; Developmental programing; Leptin; Maternal exposure to PM2.5; Obesity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adiposity
  • Age Factors
  • Animals
  • Birth Weight
  • DNA Methylation
  • Eating
  • Feeding Behavior
  • Female
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Hypothalamus / metabolism
  • Hypothalamus / physiopathology
  • Lactation
  • Leptin / blood
  • Leptin / genetics
  • Male
  • Maternal Exposure*
  • Mice, Inbred C57BL
  • Neuropeptide Y / metabolism
  • Obesity / chemically induced*
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology
  • Particulate Matter / administration & dosage
  • Particulate Matter / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Pro-Opiomelanocortin / metabolism
  • Promoter Regions, Genetic
  • Risk Assessment
  • Sex Factors
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • Weight Gain

Substances

  • Leptin
  • Neuropeptide Y
  • Particulate Matter
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Pro-Opiomelanocortin