Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action
Autor: | Robert E. McGehee, Vijayalakshmi Varma, Neda Rasouli, Cathy M. Gurley, Greg T. Nolen, Bounleut Phanavanh, Charlotte A. Peterson, Tasha Starks, Aiwei Yao-Borengasser, Philip A. Kern, Pippa Simpson |
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Rok vydání: | 2009 |
Předmět: |
Adult
medicine.medical_specialty Physiology Myoblasts Skeletal Endocrinology Diabetes and Metabolism Adipose tissue macrophages Muscle Fibers Skeletal Palmitic Acid Gene Expression Adipose tissue Inflammation Cell Communication Fatty Acids Nonesterified Young Adult Insulin resistance Physiology (medical) Internal medicine medicine Humans Insulin Myocyte Obesity Cells Cultured Myositis biology Macrophages Skeletal muscle Articles Fibroblasts Middle Aged medicine.disease Coculture Techniques Muscle atrophy Insulin receptor Endocrinology medicine.anatomical_structure biology.protein Cytokines Insulin Resistance medicine.symptom Signal Transduction |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 296:E1300-E1310 |
ISSN: | 1522-1555 0193-1849 |
Popis: | Obesity is characterized by adipose tissue expansion as well as macrophage infiltration of adipose tissue. This results in an increase in circulating inflammatory cytokines and nonesterified fatty acids, factors that cause skeletal muscle insulin resistance. Whether obesity also results in skeletal muscle inflammation is not known. In this study, we quantified macrophages immunohistochemically in vastus lateralis biopsies from eight obese and eight lean subjects. Our study demonstrates that macrophages infiltrate skeletal muscle in obesity, and we developed an in vitro system to study this mechanistically. Myoblasts were isolated from vastus lateralis biopsies and differentiated in culture. Coculture of differentiated human myotubes with macrophages in the presence of palmitic acid, to mimic an obese environment, revealed that macrophages in the presence of palmitic acid synergistically augment cytokine and chemokine expression in myotubes, decrease IκB-α protein expression, increase phosphorylated JNK, decrease phosphorylated Akt, and increase markers of muscle atrophy. These results suggest that macrophages alter the inflammatory state of muscle cells in an obese milieu, inhibiting insulin signaling. Thus in obesity both adipose tissue and skeletal muscle inflammation may contribute to insulin resistance. |
Databáze: | OpenAIRE |
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