Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue
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Date
2022-08
Publication Type
Journal Article
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yes
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Abstract
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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published
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Journal / series
Volume
54
Pages / Article No.
102353
Publisher
Elsevier
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Edition / version
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Subject
Obesity; Metabolic plasticity; Visceral adipose tissue; Mitochondrial dysfunction; Exercise; Caloric restriction; Multi-organ approach; Human obesity; Two-steps bariatric surgery; Metabolic fingerprint
Organisational unit
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)