Back to Search
Start Over
A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2016 Nov; Vol. 60 (11), pp. 2421-2432. Date of Electronic Publication: 2016 Sep 08. - Publication Year :
- 2016
-
Abstract
- Scope: 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.<br />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-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.<br />Conclusion: This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1β secretion and improved insulin signaling.<br /> (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- 3T3-L1 Cells
Animals
Cytokines metabolism
Diabetes Mellitus, Type 2 diet therapy
Diet, High-Fat adverse effects
Hyperglycemia metabolism
Inflammation metabolism
Insulin metabolism
Insulin Resistance physiology
Interleukin-1beta metabolism
Interleukin-6 metabolism
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein
NLR Proteins
Tumor Necrosis Factor-alpha drug effects
Tumor Necrosis Factor-alpha metabolism
Adipose Tissue metabolism
Caseins pharmacology
Inflammasomes metabolism
Obesity metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 60
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 27390025
- Full Text :
- https://doi.org/10.1002/mnfr.201501054