Perinatal nicotine exposure increases obesity susceptibility by peripheral leptin resistance in adult female rat offspring

Toxicol Lett. 2018 Feb:283:91-99. doi: 10.1016/j.toxlet.2017.11.015. Epub 2017 Nov 28.

Abstract

Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue.

Keywords: Lipogenesis; Lipolysis; Nicotine; Obesity; Peripheral leptin resistance.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / ultrastructure
  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Cell Size / drug effects
  • Female
  • Gene Expression / drug effects
  • Intra-Abdominal Fat / drug effects
  • Leptin / metabolism*
  • Lipolysis / genetics
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Nicotine / toxicity*
  • Nicotinic Agonists / toxicity*
  • Obesity / chemically induced*
  • Obesity / metabolism*
  • Pregnancy
  • Rats
  • Rats, Wistar

Substances

  • Leptin
  • Nicotinic Agonists
  • Nicotine