title: A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling.
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. 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 insulin resistance.
  
  
  
  J774.2 macrophages were LPS primed (10 ng/mL) and stimulated with adenosine triphosphate (5 mM) to assess NLRP3 inflammasome activity. Pretreatment with CH (1 mg/mL; 48 h) reduced caspase-1 activity and decreased IL-1β secretion from J774.2 macrophages in vitro. 3T3-L1 adipocytes cultured with conditioned media from CH-pretreated 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 wk ± 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 cultured ex vivo. CH supplementation attenuated IL-1β, tumor necrosis factor alpha (TNF-α) and IL-6 secretion from AT and IL-1β, IL-18, and TNF-α from bone marrow macrophages following adenosine triphosphate stimulation ex vivo.
  
  
  
  This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1β secretion and improved insulin signaling.
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Niamh P
authors.initials: NP
authors.lastname: Healy
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kirwan
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Maeve A
authors.initials: MA
authors.lastname: McArdle
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: Holohan
authors.affiliation: Department of Life Sciences and Food for Health Ireland (FHI), University of Limerick, Castletroy, Limerick, Ireland.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Nongonierma
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Keane
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Stacey
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Celkova
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Lyons
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McGillicuddy
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Orla M
authors.initials: OM
authors.lastname: Finucane
authors.affiliation: Teagasc Food Research Centre, Moorepark and Food for Health Ireland (FHI), Fermoy, County Cork, Ireland.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Murray
authors.affiliation: Teagasc Food Research Centre, Moorepark and Food for Health Ireland (FHI), Fermoy, County Cork, Ireland.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kelly
authors.affiliation: Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: Department of Life Sciences and Food for Health Ireland (FHI), University of Limerick, Castletroy, Limerick, Ireland.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: FitzGerald
authors.affiliation: Nutrigenomics Research Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Institute of Food and Health, University College Dublin, Dublin, Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002364:Caseins / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy; D059305:Diet, High-Fat / Q000009:adverse effects; D006943:Hyperglycemia / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D009765:Obesity / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D002364:Caseins; D016207:Cytokines; D058847:Inflammasomes; D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C492716:Nlrp3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C475729:casein hydrolysate
keywords: Adipose tissue; Functional food; Inflammation; Obesity; Type 2 diabetes