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Diabetes. 2015 Jun;64(6):2116-28. doi: 10.2337/db14-1098. Epub 2015 Jan 27.

Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity.

Author information

1
Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
2
School of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
3
Inflammatory Research Group, Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
4
Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
5
Department of Dietetics and Human Nutrition, La Trobe University, Melbourne, Victoria, Australia.
6
The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
7
Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, and CIBER Phyisiopathology of Obesity and Nutrition (CIBEROBN), University of Córdoba, Córdoba, Spain.
8
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.

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.

PMID:
25626736
DOI:
10.2337/db14-1098
[Indexed for MEDLINE]
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