Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus

Abstract

Increased plasma non-esterified fatty acids (NEFAs) link obesity with insulin resistance and type 2 diabetes mellitus (T2DM). However, in contrast to the saturated FA (SFA) palmitic acid, the monounsaturated FA (MUFA) oleic acid elicits beneficial effects on insulin sensitivity, and the dietary palmitic acid:oleic acid ratio impacts diabetes risk in humans. Here we review recent mechanistic insights into the beneficial effects of oleic acid compared with palmitic acid on insulin resistance and T2DM, including its anti-inflammatory actions, and its capacity to inhibit endoplasmic reticulum (ER) stress, prevent attenuation of the insulin signaling pathway, and improve β cell survival. Understanding the molecular mechanisms of the antidiabetic effects of oleic acid may contribute to understanding the benefits of this FA in the prevention or delay of T2DM.

FAM3A plays crucial roles in controlling PDX1 and insulin expressions in pancreatic beta cells

“…Clearly, inhibition of FAM3A‐CaM‐FOXA2 axis links mitochondrial dysfunction to PDX1 repression and pancreatic β cell dysfunction under obese condition. It has long been known that saturated fatty acid such as palmitate exerts deleterious effects, whereas unsaturated fatty acid such as oleate has beneficial effects on pancreatic β cell functions . Activation of miR‐423‐5p to repress FAM3A signaling pathway provides a novel explanation for palmitate‐induced nuclear exclusion of FOXA2 in pancreatic β cells .…”

“…It has long been known that saturated fatty acid such as palmitate exerts deleterious effects, whereas unsaturated fatty acid such as oleate has beneficial effects on pancreatic β cell functions. 61,62 Activation of miR-423-5p to repress FAM3A signaling pathway provides a novel explanation for palmitate-induced nuclear exclusion of FOXA2 in pancreatic β cells. 32 Moreover, activation of FAM3A expression is also a novel mechanism for explaining oleate's beneficial effects on pancreatic β cell functions.…”

Flaxseed Oil or n‐7 Fatty Acid‐Enhanced Fish Oil Supplementation Alters Fatty Acid Composition, Plasma Insulin and Serum Ceramide Concentrations, and Gene Expression in Lambs

“…While the exact mechanism by which palmitoleic acid could reduce ceramide synthesis is not known, we hypothesize that it can exert similar ceramide‐lowering effects similar to other MUFA like oleic acid (Jin et al, ). Oleic acid reduces ceramide accumulation with the simultaneous induction of mitochondrial FA oxidation and the reduction of inflammatory signals, both of which can improve insulin signaling (Palomer et al, ). In support, palmitoleic acid has a demonstrated ability to reduce inflammation and to improve insulin sensitivity (Chan et al, ; Dimopoulos et al, ).…”

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

“…Mitochondrial fragmentation, a major producer of ROS, occurs frequently during PA-caused apoptosis. [25] This motivated us to monitor the mitochondrial state in INS-1E cells after sequential treatment with chiral G@SeNPs and PA. As shown in Figure 3 e, the mitochondria in healthy INS-1E cells were randomly distributed throughout the cytoplasm, while after treatment with PA there was evident mitochondrial fragmentation, indicated by the white arrows in INS-1E cells image. However, pretreatment with the chiral G@SeNPs effectively prevented the PA-caused mitochondrial fragmen-tation, and specifically, l-G@SeNPs demonstrated a stronger preventative effect than d-G@SeNPs and dl-G@SeNPs.…”