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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #277077
Title: The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism

Author
item Dekrey, Emilie
item Picklo, Matthew

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Review Article
Publication Acceptance Date: 3/13/2012
Publication Date: 7/15/2012
Citation: Dekrey, E.E., Picklo, M.J. 2012. The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism. Journal of Nutritional Biochemistry. 23:1201-1206.

Interpretive Summary: The cellular protein Nrf2 allows the body’s cells to respond to oxidative stress. The Nrf2 pathway has nutritional interest owing to its activation by chemicals found in food such as sulforaphane that is found in broccoli. Recently, the Nrf2 protein was identified as having regulatory functions energy metabolism in the liver and fat tissue. Nrf2 increases energy metabolism. Lard-based, but not soybean oil-based high fat diets reduce Nrf2, suggesting a macronutrient influence on the activation of the Nrf2 pathway and susceptibility to oxidative stress. This review examines data revealing the Nrf2 pathway’s regulatory role in energy metabolism at the molecular, cellular and whole animal levels. Understanding the relationship of Nrf2 and energy metabolism in cells, tissues, and physiologic systems will provide novel insights for nutritional interventions for obesity and its co-morbidities such as diabetes.

Technical Abstract: The nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that responds to oxidative stress by binding to the antioxidant response element (ARE) in the promoter of genes coding for antioxidant enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1) and proteins for glutathione synthesis. The Nrf2/ARE pathway has nutritional interest owing to its activation by phytochemicals such as sulforaphane. Recently, the Nrf2 pathway was identified as having regulatory functions in mitochondrial biogenesis, adipocyte differentiation, and liver energy metabolism. Activation of Nrf2 increases energy metabolism and conversely suppresses lipid synthesis. Lard-based, but not soybean oil-based high fat diets reduce mRNA expression of Nrf2 and its downstream targets, suggesting a macronutrient influence on the activation of the Nrf2 pathway and susceptibility to oxidative stress. This review examines data revealing the Nrf2 pathway’s regulatory role in energy metabolism at the molecular, cellular and whole animal levels. Understanding the relationship of Nrf2 and energy metabolism in cells, tissues, and physiologic systems will provide novel insights for nutritional interventions for obesity and its co-morbidities such as diabetes.