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.

Metabolite profiling paradoxically reveals favorable levels of lipids, markers of oxidative stress and unsaturated fatty acids in a diabetes susceptible group of Middle Eastern immigrants

“…These differences were also reflected in levels of acylcarnitines; saturated acylcarnitine (14:0) which showed lower levels and polyunsaturated (14:2 and 18:2) higher levels in Iraqi immigrants. Moreover, HOMA-beta was higher in the Iraqi population, which is in line with a vast number of in vitro studies, suggesting unsaturated fatty acids to improve beta-cell function [19]. Prolonged fasting has been shown to increase levels of polyunsaturated fatty acids and unsaturated acylcarnitines more than those of the saturated intermediates [20].…”

Liraglutide protects against glucolipotoxicity‐induced RIN‐m5F β‐cell apoptosis through restoration of PDX1 expression

“…Prolonged exposure to hyperglycaemia and hyperlipidemia can induce cell and tissue damage, also known as glucotoxicity and lipotoxicity respectively . Interestingly, hyperlipidemia is characterized by an increase in circulating free fatty acids (FFA), which is recognized as a major driving force for insulin resistance and results in constantly high blood sugar levels . Thus, hyperglycaemia seems to work synergistically with hyperlipidemia via a process referred to as glucolipotoxicity, which contributes to various cellular dysfunctions, including endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction and chronic low‐grade inflammation .…”

Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes

“…Saturated FFA incorporation into membranes reduces fluidity, which can inhibit transmembrane proteins such as SERCA [145], impacting Ca 2+ shuttling back into the ER [135,146]. The reduction in fluidity can also increase ER stress markers independent of SERCA [147,148]. ER stress activates the unfolded protein response (UPR), whose end result is either the recruitment of additional chaperone proteins to mitigate the stress or the induction of apoptosis.…”