n-3 Polyunsaturated fatty acids protect against pancreaticβ-cell damage due to ER stress and prevent diabetes development.
Mol Nutr Food Res. 2015 Jun 15. Epub 2015 Jun 15. PMID: 26080997
SCOPE: In this study, we focus on the effects of n-3 polyunsaturated fatty acids (PUFAs) on tunicamycin-, streptozotocin-, or high fat diet (HFD)-inducedβ-cell damage and dysfunction.
MATERIALS AND METHODS: Pretreatment with n-3 PUFAs protected RINm5F cells and mouse islets against tunicamycin-inducedβ-cell damage through suppression of ER stress and apoptosis induction. This protective effect of n-3 PUFAs on β-cells was further demonstrated by the normalization of insulin secretion in response to glucose in tunicamycin-treated islets. In multiple low-dose streptozotocin-induced diabetes models, fat-1 mice, which endogenously synthesize n-3 PUFAs from n-6 PUFAs, were fully resistant to the development of diabetes, with normal islet morphology, high insulin immunoreactivity, and decreased apoptotic cells. In HFD-induced diabetes models, fat-1 mice also exhibited improved glucose toleranceand functional β-cell mass. In both diabetes models, we observed an attenuation of ER stress in fat-1 mice. Interestingly, n-3 PUFAs attenuated the nuclear translocation of lipogenic transcription factors sterol regulatory element-binding protein-1 (SREBP-1) and C/EBPβ, induced by tunicamycin orHFD, suggesting that n-3 PUFAs suppress ER stress via modulation of SREBP-1 and C/EBPβ.
CONCLUSION: Together, these results suggest that n-3 PUFAs block ER stress, thus protectingβ cells against diabetogenic insult; therefore, dietary supplementation of n-3 PUFAs has therapeutic potential for the preservation of functional β-cell mass.