Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity

被引:36
作者
Lopez-Domenech, Sandra [1 ]
Abad-Jimenez, Zaida [1 ]
Iannantuoni, Francesca [1 ]
de Maranon, Aranzazu M. [1 ]
Rovira-Llopis, Susana [1 ]
Morillas, Carlos [1 ]
Banuls, Celia [1 ]
Manuel Victor, Victor [1 ,2 ,3 ]
Rocha, Milagros [1 ,2 ]
机构
[1] Univ Hosp Doctor Peset FISABIO, Dept Endocrinol & Nutr, Avda Gaspar Aguilar 90, Valencia 46017, Spain
[2] Univ Valencia, CIBER CB06 04 0071 Res Grp, CIBER Hepat & Digest Dis, Av Blasco Ibanez 13, Valencia 46010, Spain
[3] Univ Valencia, Dept Physiol, Av Blasco Ibanez 13, Valencia 46010, Spain
关键词
Diet; Inflammation; Endoplasmic reticulum; Oxidative stress; Mitochondria; INSULIN-RESISTANCE; ADIPOSE-TISSUE; METABOLIC SYNDROME; ER STRESS; EXPRESSION; PROTEIN; COMPLEMENT; JNK; C3; INFLAMMATION;
D O I
10.1016/j.molmet.2018.10.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: In obese patients undergoing caloric restriction, there are several potential mechanisms involved in the improvement of metabolic outcomes. The present study further explores whether caloric restriction can modulate endoplasmic reticulum (ER) stress and mitochondrial function, as both are known to be mechanisms underlying inflammation and insulin resistance (IR) during obesity. Methods: A total of 64 obese patients with BMI >= 35 kg/m(2) underwent a dietary program consisting of 6 weeks of a very-low-calorie diet followed by 18 weeks of low-calorie diet. We evaluated changes in the metabolic and inflammatory markers -TNF alpha, hsCRP, complement component 3 (C3c), and retinol binding protein 4 (RBP4)-, in the ER stress markers and modulators -eIF2 alpha-P, sXBP1, ATF6, JNK-P, CHOP, GRP78, and SIRT1-, and in mitochondrial function parameters-mitochondrial reactive oxygen species (mROS), glutathione peroxidase 1 (GPX1), cytosolic Ca2+, and mitochondrial membrane potential. Results: The dietary intervention produced an 8.85% weight loss associated with enhanced insulin sensitivity, a less marked atherogenic lipid profile, and a decrease in systemic inflammation (TNF alpha, hsCRP) and adipokine levels (RBP4 and C3c). Chronic ER stress was significantly reduced (ATF6-CHOP, JNK-P) and expression levels of SIRT1 and GRP78 - a Ca2+-dependent chaperone - were increased and accompanied by the restoration of Ca2+ depots. Furthermore, mROS production and mitochondrial membrane potential improvement were associated with the up-regulation of the antioxidant enzyme GPX1. Conclusions: Our data provide evidence that moderate weight loss attenuates systemic inflammation and IR and promotes the amelioration of ER stress and mitochondrial dysfunction, increasing the expression of chaperones, SIRT1 and antioxidant GPX1. (C) 2018 The Authors. Published by Elsevier GmbH.
引用
收藏
页码:24 / 33
页数:10
相关论文
共 56 条
[1]   C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells [J].
Allagnat, F. ;
Fukaya, M. ;
Nogueira, T. C. ;
Delaroche, D. ;
Welsh, N. ;
Marselli, L. ;
Marchetti, P. ;
Haefliger, J. A. ;
Eizirik, D. L. ;
Cardozo, A. K. .
CELL DEATH AND DIFFERENTIATION, 2012, 19 (11) :1836-1846
[2]   Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans [J].
Anderson, Ethan J. ;
Lustig, Mary E. ;
Boyle, Kristen E. ;
Woodlief, Tracey L. ;
Kane, Daniel A. ;
Lin, Chien-Te ;
Price, Jesse W., III ;
Kang, Li ;
Rabinovitch, Peter S. ;
Szeto, Hazel H. ;
Houmard, Joseph A. ;
Cortright, Ronald N. ;
Wasserman, David H. ;
Neufer, P. Darrell .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (03) :573-581
[3]   Classification and Diagnosis of Diabetes [J].
不详 .
DIABETES CARE, 2015, 38 :S8-S16
[4]   Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes [J].
Arruda, Ana Paula ;
Hotamisligil, Goekhan S. .
CELL METABOLISM, 2015, 22 (03) :381-397
[5]   Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals [J].
Banuls, C. ;
Rovira-Llopis, S. ;
Lopez-Domenech, S. ;
Diaz-Morales, N. ;
Blas-Garcia, A. ;
Veses, S. ;
Morillas, C. ;
Victor, V. M. ;
Rocha, M. ;
Hernandez-Mijares, A. .
INTERNATIONAL JOURNAL OF OBESITY, 2017, 41 (10) :1556-1563
[6]   Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects [J].
Chattopadhyay, Mrittika ;
Khemka, Vineet Kumar ;
Chatterjee, Gargi ;
Ganguly, Anirban ;
Mukhopadhyay, Satinath ;
Chakrabarti, Sasanka .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2015, 399 (1-2) :95-103
[7]   Cab45S inhibits the ER stress-induced IRE1-JNK pathway and apoptosis via GRP78/BiP [J].
Chen, L. ;
Xu, S. ;
Liu, L. ;
Wen, X. ;
Xu, Y. ;
Chen, J. ;
Teng, J. .
CELL DEATH & DISEASE, 2014, 5 :e1219-e1219
[8]   Downregulation of the Longevity-Associated Protein Sirtuin 1 in Insulin Resistance and Metabolic Syndrome: Potential Biochemical Mechanisms [J].
de Kreutzenberg, Saula Vigili ;
Ceolotto, Giulio ;
Papparella, Italia ;
Bortoluzzi, Alessia ;
Semplicini, Andrea ;
Dalla Man, Chiara ;
Cobelli, Claudio ;
Fadini, Gian Paolo ;
Avogaro, Angelo .
DIABETES, 2010, 59 (04) :1006-1015
[9]   Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats [J].
Ding, Shibin ;
Jiang, Jinjin ;
Zhang, Guofu ;
Bu, Yongjun ;
Zhang, Guanghui ;
Zhao, Xiangmei .
PLOS ONE, 2017, 12 (08)
[10]   Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis [J].
Erbay, Ebru ;
Babaev, Vladimir R. ;
Mayers, Jared R. ;
Makowski, Liza ;
Charles, Khanichi N. ;
Snitow, Melinda E. ;
Fazio, Sergio ;
Wiest, Michelle M. ;
Watkins, Steven M. ;
Linton, MacRae F. ;
Hotamisligil, Goekhan S. .
NATURE MEDICINE, 2009, 15 (12) :1383-U5