A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling.
Mol Nutr Food Res
; 60(11): 2421-2432, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27390025
ABSTRACT
SCOPE Activation of the nod-like receptor protein 3 (NLRP3) inflammasome is required for IL-1ß 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-1ß 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-1ß 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-1ß, tumor necrosis factor alpha (TNF-α) and IL-6 secretion from AT and IL-1ß, IL-18, and TNF-α 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-1ß secretion and improved insulin signaling.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Caseínas
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Tecido Adiposo
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Inflamassomos
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Obesidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article