Dairy‐derived bioactive fatty acids improve pancreatic ß‐cell function

Abstract

Recent studies suggest that diets rich in dairy products protect against type 2 diabetes. The principal constituents responsible are thought to be bioactive lipids, in particular trans‐palmitoleic acid (trans‐9 16:1; TPA), although the nature of this protection is unknown. We have recently identified another milk‐derived fatty acid (FA) that may be, in part, responsible for these effects: 15‐methyl‐hexadecanoic acid, a branched‐chain FA (iso 17:0; MHA). Using the INS‐1 ß‐cell line to examine chronic effects of hyperglycemia, we characterized these two FAs with respect to altering levels of the key ß‐cell transcription factor, Pdx1. INS‐1 cells subjected to chronic high glucose (20 mM) for 24‐72 h exhibited ~50% reduced Pdx1 levels. At 24 h, neither MHA, TPA, or MHA+TPA (each at 10 μm) affected Pdx1; however, under basal (5.5 mM) glucose conditions, both TPA and MHA+TPA increased Pdx1. By 48 h, MHA supplementation markedly increased Pdx1 levels in high glucose cultures (2.6‐fold). Accordingly, 72 h cultures with 20 mM glucose + MHA maintained modestly elevated Pdx1 levels (1.25‐fold). We have previously shown that ß‐cell PPARγ regulates pdx1 expression. Positive MHA‐specific effects on Pdx1 protein levels under hyperglycemic conditions are transcriptionally conferred as demonstrated by a 2‐fold enhancement of activity in a pdx1 reporter assay. Similarly, both MHA and TPA elicited ~2‐fold increases in pparγ activity. Collectively, these data demonstrate distinct and potentially complementary bioactivities of dairy‐derived MHA and TPA. We postulate that a key target of these bioactive FAs responsible for modulating diabetes risk is the pancreatic ß‐cell.