Perfluorooctanoic acid exposure disturbs glucose metabolism in mouse liver

Toxicol Appl Pharmacol. 2017 Nov 15;335:41-48. doi: 10.1016/j.taap.2017.09.019. Epub 2017 Sep 23.

Abstract

Environmental pollutants such as perfluorooctanoic acid (PFOA) can influence human metabolism processes and are associated with certain metabolic diseases. To investigate the effect of PFOA on liver glucose homeostasis, adult male Balb/c mice were orally administered 1.25mg/kg of PFOA for 28d consecutively. Compared with the control mice, the body weights of the PFOA-treated mice were unchanged following exposure. However, PFOA exposure increased fasting blood glucose levels and decreased glycogen and glucose content in the liver of treated mice, but did not influence blood insulin significantly. The increased blood glucagon might contribute to the hyperglycemia observed in the PFOA-treated group compared with the control group. In addition, pyruvate tolerance tests supported enhanced glucose production ability in PFOA-exposed mice. Consistent with the increase in blood glucose and decrease in hepatic glucose and glycogen, PFOA exposure decreased the protein level of glycogen synthase in the mouse liver, but increased the level of glucokinase. Furthermore, liver pyruvate, as well as mRNA levels of enzymes involved in the Krebs cycle, such as citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, increased in the PFOA-treated group. PFOA exposure did not affect muscle glucose or glycogen levels. Indirect calorimetry showed higher VO2 consumption and respiratory quotient values in the PFOA-treated group compared with the control group, implying that PFOA treatment might promote energy consumption in mice, with a reliance on carbohydrates as a primary source of energy. Thus, our findings indicate that subacute exposure to PFOA might enhance glycogenolysis and gluconeogenesis and promote carbohydrate consumption.

Keywords: Blood glucose; Metabolism; Perfluorooctanoic acid; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Calorimetry, Indirect
  • Caprylates / toxicity*
  • Energy Metabolism / drug effects*
  • Environmental Pollutants / toxicity*
  • Fluorocarbons / toxicity*
  • Gene Expression Regulation, Enzymologic
  • Gluconeogenesis / drug effects
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism
  • Glycogen / metabolism
  • Glycogenolysis / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice, Inbred BALB C
  • Oxygen Consumption / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors

Substances

  • Biomarkers
  • Blood Glucose
  • Caprylates
  • Environmental Pollutants
  • Fluorocarbons
  • Glucose Transport Proteins, Facilitative
  • RNA, Messenger
  • Glycogen
  • perfluorooctanoic acid