PMID- 25397888 OWN - NLM STAT- MEDLINE DCOM- 20151218 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 11 DP - 2014 TI - Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat. PG - e112813 LID - 10.1371/journal.pone.0112813 [doi] LID - e112813 AB - 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-alpha (TNF-alpha), 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 degrees 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. FAU - Yamaoka, Masaya AU - Yamaoka M AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Maeda, Norikazu AU - Maeda N AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Takayama, Yasunori AU - Takayama Y AD - Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan. FAU - Sekimoto, Ryohei AU - Sekimoto R AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Tsushima, Yu AU - Tsushima Y AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Matsuda, Keisuke AU - Matsuda K AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Mori, Takuya AU - Mori T AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Inoue, Kana AU - Inoue K AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Nishizawa, Hitoshi AU - Nishizawa H AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. FAU - Tominaga, Makoto AU - Tominaga M AD - 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. FAU - Funahashi, Tohru AU - Funahashi T AD - 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. FAU - Shimomura, Iichiro AU - Shimomura I AD - Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141114 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Insulin) RN - 0 (Lipopolysaccharides) RN - 0 (Per1 protein, mouse) RN - 0 (Period Circadian Proteins) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - 3T3-L1 Cells MH - Adipose Tissue/*metabolism MH - Animals MH - Blotting, Western MH - Body Temperature MH - Catalase/genetics/metabolism MH - Cell Differentiation/drug effects MH - Chemokine CCL2/genetics/metabolism MH - Humans MH - Hydrogen Peroxide/toxicity MH - Hypothermia, Induced MH - *Inflammation MH - Insulin/pharmacology MH - Lipopolysaccharides/toxicity MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Motor Activity/drug effects MH - Obesity/metabolism/*pathology MH - Period Circadian Proteins/genetics/*metabolism MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC4232416 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/11/15 06:00 MHDA- 2015/12/19 06:00 PMCR- 2014/11/14 CRDT- 2014/11/15 06:00 PHST- 2014/07/17 00:00 [received] PHST- 2014/10/15 00:00 [accepted] PHST- 2014/11/15 06:00 [entrez] PHST- 2014/11/15 06:00 [pubmed] PHST- 2015/12/19 06:00 [medline] PHST- 2014/11/14 00:00 [pmc-release] AID - PONE-D-14-32157 [pii] AID - 10.1371/journal.pone.0112813 [doi] PST - epublish SO - PLoS One. 2014 Nov 14;9(11):e112813. doi: 10.1371/journal.pone.0112813. eCollection 2014.