Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Masaya
M
Yamaoka
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Norikazu
N
Maeda
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan.
Yasunori
Y
Takayama
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Ryohei
R
Sekimoto
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Yu
Y
Tsushima
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Keisuke
K
Matsuda
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Takuya
T
Mori
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Kana
K
Inoue
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Hitoshi
H
Nishizawa
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan; Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, 444-8585, Japan.
Makoto
M
Tominaga
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Tohru
T
Funahashi
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Iichiro
I
Shimomura
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007036:Hypothermia, Induced; D007249:Inflammation; D007328:Insulin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007328:Insulin; D008070:Lipopolysaccharides; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D051057:Proto-Oncogene Proteins c-akt