Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults

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作者
Ryosuke Shirakawa
Takayuki Nakajima
Aya Yoshimura
Yukako Kawahara
Chieko Orito
Miwako Yamane
Haruka Handa
Shingo Takada
Takaaki Furihata
Arata Fukushima
Naoki Ishimori
Masao Nakagawa
Isao Yokota
Hisataka Sabe
Satoshi Hashino
Shintaro Kinugawa
Takashi Yokota
机构
[1] Hokkaido University,Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine
[2] Hokkaido University,Health Care Center
[3] Hokkaido University,Department of Molecular Biology, Faculty of Medicine and Graduate School of Medicine and Institute for Genetic Medicine
[4] Hokkaido University,Department of Hematology, Faculty of Medicine and Graduate School of Medicine
[5] Hokkaido University,Department of Biostatistics, Faculty of Medicine and Graduate School of Medicine
[6] Kyushu University,Department of Cardiovascular Medicine, Faculty of Medical Sciences
[7] Kyushu University,Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology
[8] Hokkaido University Hospital,Institute of Health Science Innovation for Medical Care
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Systemic inflammation underlies the association between obesity and nonalcoholic fatty liver disease (NAFLD). Here, we investigated functional changes in leukocytes’ mitochondria in obese individuals and their associations with NAFLD. We analyzed 14 obese male Japanese university students whose body mass index was > 30 kg/m2 and 15 healthy age- and sex-matched lean university students as controls. We observed that the mitochondrial oxidative phosphorylation (OXPHOS) capacity with complex I + II-linked substrates in peripheral blood mononuclear cells (PBMCs), which was measured using a high-resolution respirometry, was significantly higher in the obese group versus the controls. The PBMCs’ mitochondrial complex IV capacity was also higher in the obese subjects. All of the obese subjects had hepatic steatosis defined by a fatty liver index (FLI) score ≥ 60, and there was a positive correlation between their FLI scores and their PBMCs’ mitochondrial OXPHOS capacity. The increased PBMCs’ mitochondrial OXPHOS capacity was associated with insulin resistance, systemic inflammation, and higher serum levels of interleukin-6 in the entire series of subjects. Our results suggest that the mitochondrial respiratory capacity is increased in the PBMCs at the early stage of obesity, and the enhanced PBMCs’ mitochondrial oxidative metabolism is associated with hepatic steatosis in obese young adults.
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