title: Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity.
abstract: Saturated fatty acid (SFA) high-fat diets (HFDs) enhance interleukin (IL)-1β-mediated adipose inflammation and insulin resistance. However, the mechanisms by which different fatty acids regulate IL-1β and the subsequent effects on adipose tissue biology and insulin sensitivity in vivo remain elusive. We hypothesized that the replacement of SFA for monounsaturated fatty acid (MUFA) in HFDs would reduce pro-IL-1β priming in adipose tissue and attenuate insulin resistance via MUFA-driven AMPK activation. MUFA-HFD-fed mice displayed improved insulin sensitivity coincident with reduced pro-IL-1β priming, attenuated adipose IL-1β secretion, and sustained adipose AMPK activation compared with SFA-HFD-fed mice. Furthermore, MUFA-HFD-fed mice displayed hyperplastic adipose tissue, with enhanced adipogenic potential of the stromal vascular fraction and improved insulin sensitivity. In vitro, we demonstrated that the MUFA oleic acid can impede ATP-induced IL-1β secretion from lipopolysaccharide- and SFA-primed cells in an AMPK-dependent manner. Conversely, in a regression study, switching from SFA- to MUFA-HFD failed to reverse insulin resistance but improved fasting plasma insulin levels. In humans, high-SFA consumers, but not high-MUFA consumers, displayed reduced insulin sensitivity with elevated pycard-1 and caspase-1 expression in adipose tissue. These novel findings suggest that dietary MUFA can attenuate IL-1β-mediated insulin resistance and adipose dysfunction despite obesity via the preservation of AMPK activity.
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Orla M
authors: OM
authors: Finucane
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Claire L
authors: CL
authors: Lyons
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Aoife M
authors: AM
authors: Murphy
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Clare M
authors: CM
authors: Reynolds
authors: School of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors: Rut
authors: R
authors: Klinger
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Niamh P
authors: NP
authors: Healy
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Aoife A
authors: AA
authors: Cooke
authors: Inflammatory Research Group, Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: Rebecca C
authors: RC
authors: Coll
authors: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
authors: Liam
authors: L
authors: McAllan
authors: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
authors: Kanishka N
authors: KN
authors: Nilaweera
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Marcella E
authors: ME
authors: O'Reilly
authors: Department of Dietetics and Human Nutrition, La Trobe University, Melbourne, Victoria, Australia.
authors: Audrey C
authors: AC
authors: Tierney
authors: The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
authors: Melissa J
authors: MJ
authors: Morine
authors: Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, and CIBER Phyisiopathology of Obesity and Nutrition (CIBEROBN), University of Córdoba, Córdoba, Spain.
authors: Juan F
authors: JF
authors: Alcala-Diaz
authors: Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, and CIBER Phyisiopathology of Obesity and Nutrition (CIBEROBN), University of Córdoba, Córdoba, Spain.
authors: Jose
authors: J
authors: Lopez-Miranda
authors: School of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors: Darran P
authors: DP
authors: O'Connor
authors: Inflammatory Research Group, Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: Luke A
authors: LA
authors: O'Neill
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Fiona C
authors: FC
authors: McGillicuddy
authors: Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland helen.roche@ucd.ie.
authors: Helen M
authors: HM
authors: Roche
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D005229:Fatty Acids, Monounsaturated; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases