Chronic exposure to methylmercury disrupts ghrelin actions in C57BL/6J mice

Beatriz Ferrer, Lisa M. Prince, Alexey A. Tinkov, Abel Santamaria, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalArticlepeer-review

Abstract

Methylmercury (MeHg) is a neurotoxic pollutant widely present in the environment. Initial symptoms of MeHg may include loss of body weight. However, the mechanisms by which MeHg induces body weight changes have yet to be fully elucidated. Body weight is regulated by multiple mechanisms. Whereas multiple peripheral peptides lead to food intake cessation, ghrelin is the only recognized peripheral hormone that stimulates food intake. It exerts its action on Neuropeptide Y/Agouti-related peptide neurons in the hypothalamus. To test if MeHg affects ghrelin signaling C57BL/6J mice (males and females) were exposed to 5 ppm MeHg via drinking water during a month. On days 15 and 30 of MeHg exposure ghrelin was administered intraperitoneally and changes in body weight and food intake were recorded. In addition, changes in ghrelin-induced signaling pathways in hypothalamus were also analyzed. Here, we show that in males, MeHg enhanced ghrelin-induced body weight gain by activating the AMP-activated Kinase (AMPK)/Uncoupled protein 2 (UCP2) signaling pathway. In contrast, in females, MeHg inhibited ghrelin-induced mTOR signaling activation and decreased Npy mRNA expression, thus mitigating the ghrelin-induced weight gain. Combined, our novel results demonstrate, for the first time, that MeHg disrupts the physiological functions of ghrelin differently in males and females.

Original languageEnglish (US)
Article number111918
JournalFood and Chemical Toxicology
Volume147
DOIs
StatePublished - Jan 2021

Keywords

  • Body weight
  • Hypothalamus
  • Methylmercury
  • Neurotoxicity

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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