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

作者：Healy Niamh P; Kirwan Anna M; McArdle Maeve A; Holohan Kieran; Nongonierma Alice B; Keane Deirdre; Kelly Stacey; Celkova Lucia; Lyons Claire L; McGillicuddy Fiona C; Finucane Orla M; Murray Brian A; Kelly Philip M; Brennan Lorraine; FitzGerald Richard J; Roche Helen M^*

来源：Molecular Nutrition & Food Research, 2016, 60(11): 2421-2432.

DOI：10.1002/mnfr.201501054

• Adipose tissue
• Functional food
• Inflammation
• Obesity
• Type 2 diabetes

Scope: Activation of the nod-like receptor protein 3 (NLRP3) inflammasome is required for IL-1 beta 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-1 beta secretion in adipose tissue (AT) and improve obesity-induced insulin resistance.
Methods and results: 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-1 beta 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-1 beta, tumor necrosis factor alpha (TNF-alpha) and IL-6 secretion from AT and IL-1 beta, IL-18, and TNF-alpha from bone marrow macrophages following adenosine triphosphate stimulation ex vivo.
Conclusion: This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1 beta secretion and improved insulin signaling.

• 出版日期2016-11