Increased inflammation, oxidative stress and mitochondrial respiration in brown adipose tissue from obese mice

被引:136
作者
Alcala, Martin [1 ]
Calderon-Dominguez, Maria [2 ,3 ]
Bustos, Eduviges [2 ,5 ]
Ramos, Pilar [1 ]
Casals, Nuria [4 ]
Serra, Dolors [2 ,3 ]
Viana, Marta [1 ]
Herrero, Laura [2 ,3 ]
机构
[1] Univ CEU San Pablo, Fac Farm, Madrid, Spain
[2] Univ Barcelona, IBUB, Sch Pharm & Food Sci, Dept Biochem & Physiol, E-08028 Barcelona, Spain
[3] Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, E-28029 Madrid, Spain
[4] UIC, Fac Med & Hlth Sci, Basic Sci Dept, E-08195 Barcelona, Spain
[5] Univ Barcelona, Sch Pharm & Food Sci, SDM, E-08028 Barcelona, Spain
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
INSULIN-RESISTANCE; COLD-EXPOSURE; FAT; THERMOGENESIS; DIET; ACTIVATION; EXPRESSION; MOUSE;
D O I
10.1038/s41598-017-16463-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Obesity is associated with severe metabolic diseases such as type 2 diabetes, insulin resistance, cardiovascular disease and some forms of cancer. The pathophysiology of obesity-induced metabolic diseases has been strongly related to white adipose tissue (WAT) dysfunction through several mechanisms such as fibrosis, apoptosis, inflammation, ER and oxidative stress. However, little is known of whether these processes are also present in brown adipose tissue (BAT) during obesity, and the potential consequences on mitochondrial activity. Here we characterized the BAT of obese and hyperglycemic mice treated with a high-fat diet (HFD) for 20 weeks. The hypertrophic BAT from obese mice showed no signs of fibrosis nor apoptosis, but higher levels of inflammation, ER stress, ROS generation and antioxidant enzyme activity than the lean counterparts. The response was attenuated compared with obesity-induced WAT derangements, which suggests that BAT is more resistant to the obesity-induced insult. In fact, mitochondrial respiration in BAT from obese mice was enhanced, with a 2-fold increase in basal oxygen consumption, through the upregulation of complex III of the electron transport chain and UCP1. Altogether, our results show that obesity is accompanied by an increase in BAT mitochondrial activity, inflammation and oxidative damage.
引用
收藏
页数:12
相关论文
共 48 条
[31]   Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species [J].
Rebiger, Lars ;
Lenzen, Sigurd ;
Mehmeti, Ilir .
BIOSCIENCE REPORTS, 2016, 36
[32]   High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans Effects of Cold Exposure and Adiposity [J].
Saito, Masayuki ;
Okamatsu-Ogura, Yuko ;
Matsushita, Mami ;
Watanabe, Kumiko ;
Yoneshiro, Takeshi ;
Nio-Kobayashi, Junko ;
Iwanaga, Toshihiko ;
Miyagawa, Masao ;
Kameya, Toshimitsu ;
Nakada, Kunihiro ;
Kawai, Yuko ;
Tsujisaki, Masayuki .
DIABETES, 2009, 58 (07) :1526-1531
[33]  
Saltiel AR, 2017, J CLIN INVEST, V127, P1, DOI [10.1172/JCI92035, 10.1172/jci92035]
[34]   Obesity, inflammation, and insulin resistance [J].
Shoelson, Steven E. ;
Herrero, Laura ;
Naaz, Afia .
GASTROENTEROLOGY, 2007, 132 (06) :2169-2180
[35]   Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease [J].
Shulman, Gerald I. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (12) :1131-1141
[36]   Analysis of time- dependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats [J].
So, Mandy ;
Gaidhu, Mandeep P. ;
Maghdoori, Babak ;
Ceddia, Rolando B. .
LIPIDS IN HEALTH AND DISEASE, 2011, 10
[37]   Lipid peroxidation is not a prerequisite for the development of obesity and diabetes in high-fat-fed mice [J].
Sohet, Florence M. ;
Neyrinck, Audrey M. ;
Dewulf, Evelyne M. ;
Bindels, Laure B. ;
Portois, Laurence ;
Malaisse, Willy J. ;
Carpentier, Yvon A. ;
Cani, Patrice D. ;
Delzenne, Nathalie M. .
BRITISH JOURNAL OF NUTRITION, 2009, 102 (03) :462-469
[38]   Dichotomous effects of VEGF-A on adipose tissue dysfunction [J].
Sun, Kai ;
Asterholm, Ingrid Wernstedt ;
Kusminski, Christine M. ;
Bueno, Ana Carolina ;
Wang, Zhao V. ;
Pollard, Jeffrey W. ;
Brekken, Rolf A. ;
Scherer, Philipp E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (15) :5874-5879
[39]   Adipose tissue remodeling and obesity [J].
Sun, Kai ;
Kusminski, Christine M. ;
Scherer, Philipp E. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (06) :2094-2101
[40]   Cellular bioenergetics as a target for obesity therapy [J].
Tseng, Yu-Hua ;
Cypess, Aaron M. ;
Kahn, C. Ronald .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (06) :465-481