title: Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.
abstract: Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet-fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning-related genes includingCideaandDio2. Conversely,Prdm16was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature-increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat-associated obesity and diabetes.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Sui
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seki
authors.affiliation: West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Fischer
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The TCM Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Rujie
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001831:Body Temperature; D001835:Body Weight; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000235:genetics; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism; D005234:Fatty Liver; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009929:Organ Size; D022722:Thermogenesis; D014157:Transcription Factors / Q000235:genetics; D000071256:Uncoupling Protein 1 / Q000235:genetics; D015854:Up-Regulation; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D052242:Adiponectin; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D007453:Iodide Peroxidase; D020738:Leptin; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C112510:Cidea protein, mouse; C521133:Prdm16 protein, mouse; C000604372:Ucp1 protein, mouse