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Beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK.

ABSTRACT: Activation of beta-adrenergic receptors (AR) in adipocytes triggers acute changes in metabolism that can alter patterns of gene expression. This work examined the mechanisms by which activation of hormone sensitive lipase (HSL) induces expression of inflammatory cytokines in adipocytes in vivo and model adipocytes in vitro. beta3-AR activation in mice triggered expression of inflammatory genes CCL2, IL-6, and PAI-1, as well as endoplasmic reticulum (ER) stress markers GRP78 and CHOP. Pharmacological inhibition of HSL blocked induction of inflammatory genes, but not ER stress markers. Promoting intracellular accumulation of free fatty acids (FFAs) in 3T3-L1 adipocytes increased expression of inflammatory cytokines, whereas inhibiting ceramide synthesis partly blocked PAI-1 expression, but not IL-6. Induction of inflammatory markers in vivo and in vitro was preceded by phosphorylation of p38 and JNK, and inhibition of HSL prevented activation of these kinases. Experiments with pharmacological inhibitors of specific MAP kinases demonstrated the importance of p38 MAPK as a mediator of lipolysis-induced inflammation in vivo and in vitro. Together, these results demonstrate that FFAs liberated by HSL activate p38 and JNK, and p38 mediates pro-inflammatory cytokine expression in adipose tissue.

SUBMITTER: Mottillo EP

PROVIDER: S-EPMC2906652 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK.

Mottillo Emilio P EP Shen Xiang Jun XJ Granneman James G JG

Biochimica et biophysica acta 20100507 9

Activation of beta-adrenergic receptors (AR) in adipocytes triggers acute changes in metabolism that can alter patterns of gene expression. This work examined the mechanisms by which activation of hormone sensitive lipase (HSL) induces expression of inflammatory cytokines in adipocytes in vivo and model adipocytes in vitro. beta3-AR activation in mice triggered expression of inflammatory genes CCL2, IL-6, and PAI-1, as well as endoplasmic reticulum (ER) stress markers GRP78 and CHOP. Pharmacolog ...[more]

PMID: 20435159

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Dataset Information

Beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK.

Publications

beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK.

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