TY - JOUR
T1 - Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction
AU - Gonzalez-Hurtado, Elsie
AU - Lee, Jieun
AU - Choi, Joseph
AU - Selen Alpergin, Ebru S.
AU - Collins, Samuel L.
AU - Horton, Maureen R.
AU - Wolfgang, Michael J.
N1 - Funding Information:
This work was supported in part by National Institute of Neurological Disorders and Stroke Grant R01 NS-072241 and American Diabetes Association Grant 1-16-IBS-313 to M. J. Wolfgang. E. Gonzalez-Hurtado was supported by Johns Hopkins Postbaccalaureate Research Education Program Grant R25 GM-109441. M. R. Horton was supported in part by National Heart, Lung, and Blood Institute Grants PO1 HL-010342 and R21 HL-111783.
Publisher Copyright:
© 2017 the American Physiological Society.
PY - 2017/5
Y1 - 2017/5
N2 - Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 MΦ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 MΦ-KO bone marrow-derived macrophages displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet-induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although IL-4-stimulated alternatively activated macrophages upregulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative, rather than causative, role in systemic metabolic dysfunction.
AB - Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 MΦ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 MΦ-KO bone marrow-derived macrophages displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet-induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although IL-4-stimulated alternatively activated macrophages upregulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative, rather than causative, role in systemic metabolic dysfunction.
KW - Adipose tissue
KW - Fatty acid
KW - Inflammation
KW - Macrophage
KW - Obesity
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U2 - 10.1152/ajpendo.00408.2016
DO - 10.1152/ajpendo.00408.2016
M3 - Article
C2 - 28223293
AN - SCOPUS:85018724259
SN - 0193-1849
VL - 312
SP - E381-E393
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -