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Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics.

ABSTRACT: Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics. Macrophage infiltration of adipose tissue and the chronic low-grade production of inflammatory cytokines have been mechanistically linked to the development of insulin resistance, the forerunner of type 2 diabetes mellitus. In this study, we evaluated the chronic effects of TNF?, IL-6, and IL-1? on adipocyte mitochondrial metabolism and morphology using the 3T3-L1 model cell system. TNF? treatment of cultured adipocytes led to significant changes in mitochondrial bioenergetics, including increased proton leak, decreased ??m, increased basal respiration, and decreased ATP turnover. In contrast, although IL-6 and IL-1? decreased maximal respiratory capacity, they had no effect on ??m and varied effects on ATP turnover, proton leak, or basal respiration. Only TNF? treatment of 3T3-L1 cells led to an increase in oxidative stress (as measured by superoxide anion production and protein carbonylation) and C16 ceramide synthesis. Treatment of 3T3-L1 adipocytes with cytokines led to decreased mRNA expression of key transcription factors and control proteins implicated in mitochondrial biogenesis, including PGC-1? and eNOS as well as deceased expression of COX IV and Cyt C. Whereas each cytokine led to effects on expression of mitochondrial markers, TNF? exclusively led to mitochondrial fragmentation and decreased the total level of OPA1 while increasing OPA1 cleavage, without expression of levels of mitofusin 2, DRP-1, or mitofilin being affected. In summary, these results indicate that inflammatory cytokines have unique and specialized effects on adipocyte metabolism, but each leads to decreased mitochondrial function and a reprogramming of fat cell biology.

SUBMITTER: Hahn WS

PROVIDER: S-EPMC4010657 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics.

Hahn Wendy S WS Kuzmicic Jovan J Burrill Joel S JS Donoghue Margaret A MA Foncea Rocio R Jensen Michael D MD Lavandero Sergio S Arriaga Edgar A EA Bernlohr David A DA

American journal of physiology. Endocrinology and metabolism 20140304 9

Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics. Macrophage infiltration of adipose tissue and the chronic low-grade production of inflammatory cytokines have been mechanistically linked to the development of insulin resistance, the forerunner of type 2 diabetes mellitus. In this study, we evaluated the chronic effects of TNFα, IL-6, and IL-1β on adipocyte mitochondrial metabolism and morphology using the 3T3-L1 model cell syst ...[more]

PMID: 24595304

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Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics.

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Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics.

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