2 Current Diabetes Reviews, 2012, 8, 2-17 1875-6417/12 $58.00+.00 © 2012 Bentham Science Publishers Dietary Fatty Acids in Metabolic Syndrome, Diabetes and Cardiovascular Diseases Giuseppe Cascio 1 , Gabriella Schiera 2 and Italia Di Liegro 2, * 1 Professor Emeritus of Infectious Diseases, School of Medicine, and 2 Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Scienze Biochimiche, Università degli Studi di Palermo, Palermo, Italy Abstract: In the last few decades, the prevalence of overweight and essential obesity has been undergoing a fast and progressive worldwide increase. Obesity has been in turn linked to type II diabetes, with the total number of diabetic patients worryingly increasing, in the last fifteen years, suggesting a pandemic phenomenon. At the same time, an increase in the prevalence of cardiovascular diseases has been also recorded. Increasing evidence suggests that the diet is involved in such escalation. In particular, the progressive globalization of food industry allowed massive supply, at a relatively low price, of a great variety of pre-packed food and bakery products, with very high energy content. Most of this food contains high amounts of saturated fatty acids (SFA) and of hydrogenated or trans fatty acids (TFA), that probably represent the prominent risk factors in the diet. Herein we will report diffusion and possible impact on health of such molecules, with reference to coronary heart disease, insulin resistance, metabolic syndrome and diabetes. We will also discuss the cellular and molecular mechanisms of action of fatty acids and fatty acid-derivatives which have been involved either in promoting or in preventing human pathologies. Free fatty acids (FFA) are not indeed only essential fuels for the organism. They also act as ligands for both membrane and nuclear receptors involved in different signaling pathways. Notably, some of these pathways can induce cell stress and apoptosis. Most important, FFA can affect glucose-induced insulin secretion and activate -cell death. These events can be at least in part counteracted by polyunsaturated fatty acids. Keywords: Fatty acids, signaling fatty acids, metabolic syndrome, type 2 diabetes, coronary heart disease (CHD), insulin resistance, FFA-dependent -cell apoptosis. 1. INTRODUCTION Since the 1990s, ever-growing evidence has been gath- ered of a progressive increase of chronic-degenerative meta- bolic diseases, that involves both industrialized- (80%) and developing- countries (20%). In particular, the prevalence of overweight and essential obesity, already present in the 1990s, has been undergoing a fast and progressive increase, with more than 1.5 billion people worldwide being thought to be obese or overweight [1]. Obesity has been in turn linked to type II diabetes (Diabetes Mellitus type 2, DM2), with the total number of diabetic patients worryingly increas- ing, in the last fifteen years, suggesting a pandemic phe- nomenon [2, 3]. At the same time, an earlier onset of cardio- vascular diseases, such as stroke, has been recorded. Is there any common cause at the basis of these disor- ders? A number of studies involve sedentary lifestyle [4] and unhealthy diet [5-7] as the main causes of different patholo- gies, the price that the humankind pays for the impressive development of technology. *Address correspondence to this author at the Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Scienze Biochimiche, Via del Vespro 29, 90127 Palermo, Italy; Tel: +39-091-23897415; Fax: +39-091-6577430; E-mail: italia.diliegro@unipa.it In the last century, indeed, two exceptional events have been acting synergistically to modify the lifestyle: i) after more than 3 million years since divergence of hominids from other primates, in a few decades only, since the 1940s, the rapid development of mechanization of production in all sectors (including the household one) caused bulky seden- tary habits in both industrialized and developing countries, with drastic reduction of physical activity; ii) in the last few decades, also a progressive mutation of feeding habit has been occurring, depending on globalization of food industry, and massive supply of pre-packed food and bakery products, with very high energy content. Most of this food contains high amounts of saturated fatty acids (SFA) and of hydro- genated or trans fatty acids (TFA), that probably represent the prominent risk factor in the diet. Although a number of epidemiologic studies have been clearly suggesting since long ago the oncogenic and/or dis- metabolic effects of SFA/TFA, the molecular mechanisms of action and the biological effects of the different classes of fatty acids remained a mistery up to recently, when the use of specific biomarkers allowed to begin analyzing the meta- bolic pathways in which fatty acids are involved, as well as evaluating their effects on different tissues, at the cellular and molecular levels. The main aim of this paper is to review representative re- sults which could contribute to shed light on this intriguing matter.