C URRENT O PINION Fatty acids regulation of inflammatory and metabolic genes Laureane N. Masi a , Alice C. Rodrigues b , and Rui Curi a Purpose of review Fatty acids influence human health and diseases in various ways. In recent years, much work has been carried out to elucidate the mechanisms by which dietary fatty acids control short-term and long-term cellular functions. We have reviewed herein the most recent studies on modulation of gene expression by fatty acids. A number of genes respond to transcription factors and present a transcription factor response element in their promoter regions. Fatty acids may exert their effects on metabolism by regulating gene transcription via transcription factors. Understanding how fatty acids control expression of metabolic genes is a promising strategy to be investigated by aiming to treat metabolic diseases such as insulin resistance, obesity, and type 2 diabetes mellitus. Recent findings Fatty acids exert many of their biological effects through the modulation of the activity of transcription factors, such as sterol regulatory element-binding proteins, peroxisome proliferator-activated receptors, and liver X receptors. Summary Fatty acid action through transcription factors controls the expression of several inflammatory and metabolic genes. Keywords liver X receptor, metabolic diseases, peroxisome proliferator-activated receptor, sterol regulatory element-binding proteins, transcription factors INTRODUCTION Metabolic syndrome is a cardiometabolic disease, characterized by dyslipidemia, glucose intolerance, hypertension, and visceral obesity. A low-grade chronic inflammatory activity is commonly observed in this disease state. Among the environ- mental factors involved in the disease, the type of dietary fat intake [saturated fatty acid (SFA), mono- unsaturated fatty acid (MUFA), or polyunsaturated fatty acids (PUFA)] has received more attention recently. Fatty acids regulate gene expression in various cells and tissues including in the adipose tissue [1], intestinal epithelial cells [2], pancreas [3], liver [4], heart [5], and leukocytes [6]. Fatty acids exert much of their effects acting as natural ligands of a number of key transcription factors, including peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), sterol- regulatory element-binding proteins (SREBPs), and carbohydrate response element-binding protein (ChREBP). These nuclear receptors respond either directly or indirectly to nutrients and metabolic cues such as cholesterol, fatty acids, glucose, and insulin to rapidly alter metabolic gene expression pro- grammes. In this review, we will highlight the recent advances in the understanding on how fatty acids ameliorate metabolic diseases and the molecular mechanisms involved. REGULATION OF GENE EXPRESSION BY FATTY ACIDS The mechanism by which fatty acids regulates gene expression remains largely unresolved. Several lines of evidence suggest that transcription factors such as a Department of Physiology and Biophysics and b Department of Pharma- cology, Institute of Biomedical Sciences, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil Correspondence to Rui Curi, Institute of Biomedical Sciences, Av. Professor Lineu Prestes, 1524, 05508–900 Sa ˜o Paulo, Brazil. Tel: +55 11 3091 7245; e-mail: ruicuri@icb.usp.br Curr Opin Clin Nutr Metab Care 2013, 16:418–424 DOI:10.1097/MCO.0b013e32836236df www.co-clinicalnutrition.com Volume 16  Number 4  July 2013 REVIEW