期刊
REDOX BIOLOGY
卷 54, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2022.102353
关键词
Obesity; Metabolic plasticity; Visceral adipose tissue; Mitochondrial dysfunction; Exercise; Caloric restriction; Multi-organ approach; Human obesity; Two-steps bariatric surgery; Metabolic fingerprint
资金
- Ministerio de Ciencia e Innovacion (MICINN) [BFU2011-24679]
- Instituto de Salud Carlos III (ISCIII) Grant [PI15/00701]
- European Regional Development Fund ``A way to build Europe'`
- Government of Catalonia Support Grups de Recerca AGAUR [2017-SGR-204, 2017-SGR-736, 2017-SGR-896]
- MINECO [RTI2018093864-B-I00, BFU2017-87958, SAF201345887-R, SAF2017-83813-C3-1-R]
- Medical University of Innsbruck Start Grant
- European Regional Development Fund
- Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la Nutricion (CIBEROBN) [CB06/03/0001]
- Government of Catalonia [2017SGR278]
- Fundacio La Marato de TV3 [201627-30]
- European Foundation for the Study of Diabetes (EFSD)/Janssen-Rising Star and L'Oreal-UNESCO For Women in Science research fellowships
- MICINN [RYC-2009-05158]
- Novo Nordisk Foundation (NNF) [NNF18CC0034900]
- Universitat de Barcelona (APIF-UB)
- SFB 1218 (DFG, German Reuter Foundation) [269925409]
- European Union [675610]
- Ministerio de Economia y Empresa (MINECO) [BES-2013-062796]
- European Research Council (ERC) [725004]
- European Research Council (ERC) [725004] Funding Source: European Research Council (ERC)
This study systematically assessed metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention, and found that there is a significant metabolic dysfunction in visceral white adipose tissue, which leads to a breakdown of metabolic plasticity.
Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.
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