Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

被引:155
作者
Malandrino, Maria Ida [1 ,2 ]
Fucho, Raquel [1 ,2 ]
Weber, Mineia [1 ,2 ]
Calderon-Dominguez, Maria [1 ,2 ]
Mir, Joan Francesc [1 ,2 ]
Valcarcel, Lorea [1 ,2 ]
Escote, Xavier [3 ,4 ]
Gomez-Serrano, Maria [2 ,5 ,6 ]
Peral, Belen [2 ,5 ,6 ]
Salvado, Laia [4 ,7 ,8 ]
Fernandez-Veledo, Sonia [3 ,4 ]
Casals, Nuria [2 ,9 ]
Vazquez-Carrera, Manuel [4 ,7 ,8 ]
Villarroya, Francesc [1 ,2 ]
Vendrell, Joan J. [3 ]
Serra, Dolors [1 ,2 ]
Herrero, Laura [1 ,2 ]
机构
[1] Univ Barcelona, Inst Biomed, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain
[2] Univ Barcelona, Inst Biomed, Fisiopatol Obesidad & Nutr, Inst Salud Carlos III, E-08028 Barcelona, Spain
[3] Univ Rovira & Virgili, Joan Univ Hosp 23, Inst Invest Sanitaria Pere & Virgili, Endocrinol & Diabet Unit, E-43007 Tarragona, Spain
[4] Univ Barcelona, Inst Biomed, Diabet & Enfermedades Metabol Asociadas, Inst Salud Carlos III, E-08028 Barcelona, Spain
[5] CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain
[6] Univ Autonoma Madrid, Madrid, Spain
[7] Univ Barcelona, Pharmacol Unit, Dept Pharmacol & Therapeut Chem, Fac Pharm, E-08028 Barcelona, Spain
[8] Univ Barcelona, Fac Pharm, Inst Biomed, E-08028 Barcelona, Spain
[9] Univ Int Catalunya, Fac Med & Hlth Sci, Dept Basic Sci, Barcelona, Spain
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2015年 / 308卷 / 09期
关键词
obesity; type; 2; diabetes; adipocytes; macrophages; inflammation; fatty acid oxidation; CPT1; ENDOPLASMIC-RETICULUM STRESS; HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; BETA-OXIDATION; CPT-I; OBESITY; CELLS; CAPACITY; DIFFERENTIATION; MITOCHONDRIA;
D O I
10.1152/ajpendo.00362.2014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CAR Delta 1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.
引用
收藏
页码:E756 / E769
页数:14
相关论文
共 53 条
[1]  
Bosello O, 2000, Obes Rev, V1, P47, DOI 10.1046/j.1467-789x.2000.00008.x
[2]   Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation - Inter-tissue and inter-species expression of CPT I and CPT II enzymes [J].
Brown, NF ;
Hill, JK ;
Esser, V ;
Kirkland, JL ;
Corkey, BE ;
Foster, DW ;
McGarry, JD .
BIOCHEMICAL JOURNAL, 1997, 327 :225-231
[3]   Overexpression of Carnitine Palmitoyltransferase-1 in Skeletal Muscle Is Sufficient to Enhance Fatty Acid Oxidation and Improve High-Fat Diet-Induced Insulin Resistance [J].
Bruce, Clinton R. ;
Hoy, Andrew J. ;
Turner, Nigel ;
Watt, Matthew J. ;
Allen, Tamara L. ;
Carpenter, Kevin ;
Cooney, Gregory J. ;
Febbraio, Mark A. ;
Kraegen, Edward W. .
DIABETES, 2009, 58 (03) :550-558
[4]   Tissue-resident macrophages [J].
Davies, Luke C. ;
Jenkins, Stephen J. ;
Allen, Judith E. ;
Taylor, Philip R. .
NATURE IMMUNOLOGY, 2013, 14 (10) :986-995
[5]   Interrelation between long-chain fatty acid oxidation rate and carnitine palmitoyltransferase 1 activity with different isoforms in rat tissues [J].
Doh, KO ;
Kim, YW ;
Park, SY ;
Lee, SK ;
Park, JS ;
Kim, JY .
LIFE SCIENCES, 2005, 77 (04) :435-443
[6]   Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters [J].
Feuerer, Markus ;
Herrero, Laura ;
Cipolletta, Daniela ;
Naaz, Afia ;
Wong, Jamie ;
Nayer, Ali ;
Lee, Jongsoon ;
Goldfine, Allison B. ;
Benoist, Christophe ;
Shoelson, Steven ;
Mathis, Diane .
NATURE MEDICINE, 2009, 15 (08) :930-U137
[7]   Increased oxidative stress in obesity and its impact on metabolic syndrome [J].
Furukawa, S ;
Fujita, T ;
Shimabukuro, M ;
Iwaki, M ;
Yamada, Y ;
Nakajima, Y ;
Nakayama, O ;
Makishima, M ;
Matsuda, M ;
Shimomura, I .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (12) :1752-1761
[8]   Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase [J].
Gao, Xuefei ;
Li, Kuai ;
Hui, Xiaoyan ;
Kong, Xiangping ;
Sweeney, Gary ;
Wang, Yu ;
Xu, Aimin ;
Teng, Maikun ;
Liu, Pentao ;
Wu, Donghai .
BIOCHEMICAL JOURNAL, 2011, 435 :723-732
[9]   Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration [J].
Gesta, Stephane ;
Bezy, Olivier ;
Mori, Marcelo A. ;
Macotela, Yazmin ;
Lee, Kevin Y. ;
Kahn, C. Ronald .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (07) :2771-2776
[10]   Involvement of de novo ceramide synthesis in pro-inflammatory adipokine secretion and adipocyte-macrophage interaction [J].
Hamada, Yoji ;
Nagasaki, Hiroshi ;
Fujiya, Atsushi ;
Seino, Yusuke ;
Shang, Qing-Long ;
Suzuki, Takeshi ;
Hashimoto, Hiroyuki ;
Oiso, Yutaka .
JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 2014, 25 (12) :1309-1316