Dietary substitution of SFA with MUFA within high-fat diets attenuates hyperinsulinaemia and pancreatic islet dysfunction
Year: 2020
Type: article
Abstract: Preliminary evidence has suggested that high-fat diets (HFD) enriched with SFA, but not MUFA, promote hyperinsulinaemia and pancreatic hypertrophy with insulin resistance. The objective of this study was to determine whether the substitution of dietary MUFA within a HFD could attenuate the progression of pancreatic islet dysfunction seen with prolonged SFA-HFD. For 32 weeks, C57BL/6J mice were fed either: (1) low-fat diet, (2) SFA-HFD or (3) SFA-HFD for 16 weeks, then switched to MUFA-HFD for 16 weeks (SFA-to-MUFA-HFD). Fasting insulin was assessed throughout the study; islets were isolated following the intervention. Substituting SFA with MUFA-HFD prevented the progression of hyperinsulinaemia observed in SFA-HFD mice (P < 0·001). Glucose-stimulated insulin secretion from isolated islets was reduced by SFA-HFD, yet not fully affected by SFA-to-MUFA-HFD. Markers of β-cell identity (Ins2, Nkx6.1, Ngn3, Rfx6, Pdx1 and Pax6) were reduced, and islet inflammation was increased (IL-1β, 3·0-fold, P = 0·007; CD68, 2·9-fold, P = 0·001; Il-6, 1·1-fold, P = 0·437) in SFA-HFD - effects not seen with SFA-to-MUFA-HFD. Switching to MUFA-HFD can partly attenuate the progression of SFA-HFD-induced hyperinsulinaemia, pancreatic inflammation and impairments in β-cell function. While further work is required from a mechanistic perspective, dietary fat may mediate its effect in an IL-1β-AMP-activated protein kinase α1-dependent fashion. Future work should assess the potential translation of the modulation of metabolic inflammation in man.
Source: British Journal Of Nutrition
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1335979935, G1635243398, Genetic and nutritional control of pancreatic beta cell identity., Roles of GWA genes in controlling pancreatic beta cell function and mass., G2040450235, G2400843396, G3499176609, Role of mitochondrial calcium transport in the regulation of insulin secretion, G3555667338, G3807423190, Dietary fatty acids: impact on inflammasome driven adipose inflammation and insulin resistance novel therapeutic targets, G4426574518, G4781795914, G480446667, All-optical deconstruction of the islet wiring patterns underlying insulin secretion in health and disease, Ligand bias at the GLP-1 receptor as a means of favouring cytoprotection, Targeting etiologic molecular mechanisms to treat human diabetes, G5877155211, The impact of long non-coding RNA at the Pax6 locus on beta cell identity and function, G6133425169, Defining the molecular and physiological mechanisms of pancreatic islet dysfunction which lead to type 2 diabetes, Role and regulation of GLP-1 receptor trafficking in pancreatic beta cells, Targeting GLP-1 receptor trafficking to improve therapies for type 2 diabetes, G7005210393, Determining the role of arcuate nucleus glucokinase in the regulation of glucose homeostasis, G7571465722, Roles of the type 2 diabetes (T2D)-associated gene C2cd4a in regulating glucose homeostasis in the mouse
OpenAlex ID: W3009459554