Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat

• Published in: PloS one 2014-11, Vol.9 (11), p.e112813-e112813
• Main Authors: Yamaoka, Masaya, Maeda, Norikazu, Takayama, Yasunori, Sekimoto, Ryohei, Tsushima, Yu, Matsuda, Keisuke, Mori, Takuya, Inoue, Kana, Nishizawa, Hitoshi, Tominaga, Makoto, Funahashi, Tohru, Shimomura, Iichiro
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipose tissue; Adipose Tissue - metabolism; AKT protein; Animal models; Animal tissues; Animals; Atherosclerosis; Blood cells; Blotting, Western; Body Temperature; Catalase; Catalase - genetics; Catalase - metabolism; Cell Differentiation - drug effects; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Circadian rhythm; Circadian rhythms; Development and progression; Diabetes; Gene expression; Genes; Homology; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Hypothermia; Hypothermia, Induced; Inflammation; Insulin; Insulin - pharmacology; Kinases; Laboratory animals; Lipopolysaccharides; Lipopolysaccharides - toxicity; Low temperature; Male; Medicine; Medicine and Health Sciences; Metabolic syndrome; Mice; Mice, Inbred C57BL; Mice, Obese; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Motor Activity - drug effects; Obesity; Obesity - metabolism; Obesity - pathology; Period 1 protein; Period Circadian Proteins - genetics; Period Circadian Proteins - metabolism; Peripheral blood; Phosphorylation; Phosphorylation - drug effects; Physiology; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Receivers & amplifiers; RNA; RNA, Messenger - metabolism; Rodents; Thermogenesis; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112813

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.