Effects of Dietary Fatty Acids in Pancreatic Beta Cell Metabolism, Implications in Homeostasis

Abstract

Fatty acids are involved in several metabolic processes, including the development of metabolic and cardiovascular diseases. In recent years a disease that has received escalated interest is type 2 diabetes (T2D). Many contributing factors including a high-caloric diet rich in dietary saturated fats have been broadly characterized as triggers of T2D. Insulin resistance resulting from a high saturated fat diet leads to alterations in lipid cellular intake and accumulation which generate lipotoxic conditions, a key phenomenon in the metabolism of β-cells. Alternatively, unsaturated fatty acids have been described to show opposite effects in pancreatic β-cells. The purpose of this work is to perform a critical analysis of the complex role of saturated and unsaturated fatty acids in β-cell metabolism. We discuss the diverse effects main dietary fatty acids have upon pancreatic β-cell metabolism as a key factor to maintain homeostasis by focusing in the cellular and molecular mechanisms involved in the development and progression of T2D. For instance, modifications in protein homeostasis as well as the intracellular management of lipid metabolism which are associated with inflammatory pathways. These conditions initiate critical metabolic rearrangements, that in turn have repercussions on insulin β-cell metabolism. This review allows an integral and broad understanding of different functions of fatty acids inside β-cells, being important metabolites for novel therapeutic targets in T2D treatment.

Keywords: fatty acids; homeostasis; lipotoxicity; type 2 diabetes.

Figure 1

Sources and metabolism of n-6 and n-3 fatty acids. On the left side, the pathway of n-6 FA is described, which begins with linoleic acid to generate arachidonic acid through the enzyme Δ⁵-desaturase. On the right side, the n-3 FA pathway starts with linolenic acid and eicosapentaenoic acid is obtained through two steps, competing for the Δ⁵-desaturase enzyme in n-6 pathway. Subsequently, docosahexaenoic acid is generated by four consequent reactions.

Figure 2

General metabolism of fatty acids in β-cells. The main metabolic pathways of FFAs are outlined in the figure, such as glycolysis, FA biosynthesis, β-oxidation. Glycolysis produces an increase in ATP, which closes K(ATP)-dependent channels and causes membrane depolarization and the opening of voltage-dependent Ca²⁺ channels, stimulating insulin release. Also, the binding of fatty acids to free fatty acid receptor 1 (FFAR1) generates changes of Ca²⁺ in ER lumen promoting insulin release in β-cell.