Journal Article


Helen M Roche
Richard J FitzGerald
Lorraine Brennan
Philip M Kelly
Brian A Murray
Orla M Finucane
Fiona C McGillicuddy
Claire L Lyons
Lucia Celkova
Stacey Kelly
and 6 others



adenosine triphosphate glucose tolerance test bone marrow insulin resistance diet high fat il 6 tumor necrosis factor adipose tissue

A casein hydrolysate protects mice against high-fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling. (2015)

Abstract Activation of the nod-like receptor protein 3 (NLRP3)-inflammasome is required for IL-1β release and is a key component of obesity-induced inflammation and insulin resistance (IR). This study hypothesized that supplementation with a casein hydrolysate (CH) would attenuate NLRP3-inflammasome mediated IL-1β secretion in adipose tissue (AT) and improve obesity-induced IR. J774.2 macrophages were LPS primed (10ng/ml) and stimulated with adenosine triphosphate (ATP) (5mM) to assess NLRP3 inflammasome activity. Pre-treatment with CH (1mg/mL; 48h) reduced caspase-1 activity and decreased IL-1β secretion from J774.2 macrophages in vitro. 3T3-L1 adipocytes cultured with conditioned media from CH pre-treated J774.2 macrophages demonstrated increased phosphorylated (p)AKT expression and improved insulin sensitivity. C57BL/6JOLaHsd mice were fed chow or high fat diet (HFD) for 12 weeks ± CH resuspended in water (0.5% w/v). CH supplementation improved glucose tolerance in HFD-fed mice as determined by glucose tolerance test. CH supplementation increased insulin-stimulated pAKT protein levels in AT, liver and muscle after HFD. Cytokine secretion was measured from AT and isolated bone marrow macrophages (BMM) cultured ex vivo. CH supplementation attenuated IL-1β, tumor necrosis factor (TNF) α and IL-6 secretion from AT and IL-1β, IL-18 and TNFα from BMM following ATP stimulation ex vivo. This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1β secretion and improved insulin signaling. This article is protected by copyright. All rights reserved.
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Full list of authors on original publication

Helen M Roche, Richard J FitzGerald, Lorraine Brennan, Philip M Kelly, Brian A Murray, Orla M Finucane, Fiona C McGillicuddy, Claire L Lyons, Lucia Celkova, Stacey Kelly and 6 others

Experts in our system

Helen M. Roche
University College Dublin
Total Publications: 105
Richard J FitzGerald
University of Limerick
Total Publications: 169
Lorraine Brennan
University College Dublin
Total Publications: 166
Brian A. Murray
Total Publications: 21
Orla M Finucane
Trinity College Dublin
Total Publications: 12
Fiona C McGillicuddy
University College Dublin
Total Publications: 19
Claire L Lyons
University College Dublin
Total Publications: 8