Parkin depletion prevents the age-related alterations in the FGF21 system and the decline in white adipose tissue thermogenic function in mice
J. physiol. biochem
; 80(1): 41-51, Feb. 2024. ilus, graf
Article
in English
| IBECS
| ID: ibc-EMG-564
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
Parkin is an ubiquitin‐E3 ligase that is involved in cellular mitophagy and was recently shown to contribute to controlling adipose tissue thermogenic plasticity. We found that Parkin expression is induced in brown (BAT) and white (WAT) adipose tissues of aged mice. We determined the potential role of Parkin in the aging-associated decline in the thermogenic capacity of adipose tissues by analyzing subcutaneous WAT, interscapular BAT, and systemic metabolic and physiological parameters in young (5 month-old) and aged (16 month-old) mice with targeted invalidation of the Parkin (Park2) gene, and their wild-type littermates. Our data indicate that suppression of Parkin prevented adipose accretion, increased energy expenditure and improved the systemic metabolic derangements, such as insulin resistance, seen in aged mice. This was associated with maintenance of browning and reduction of the age-associated induction of inflammation in subcutaneous WAT. BAT in aged mice was much less affected by Parkin gene invalidation. Such protection was associated with a dramatic prevention of the age-associated induction of fibroblast growth factor-21 (FGF21) levels in aged Parkin-invalidated mice. This was associated with a parallel reduction in FGF21 gene expression in adipose tissues and liver in aged Parkin-invalidated mice. Additionally, Parkin invalidation prevented the protein down-regulation of β-Klotho (a key co-receptor mediating FGF21 responsiveness in tissues) in aged adipose tissues. We conclude that Parkin down-regulation leads to improved systemic metabolism in aged mice, in association with maintenance of adipose tissue browning and FGF21 system functionality. (AU)
Full text:
Available
Collection:
National databases
/
Spain
Health context:
SDG3 - Health and Well-Being
/
Neglected Diseases
Health problem:
Target 3.5: Prevention and treatment of consumption of psychoactive substances
/
Tuberculosis
Database:
IBECS
Main subject:
Aging
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Adipose Tissue
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Intercellular Signaling Peptides and Proteins
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Parkinson Disease Associated Proteins
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Metabolism
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Pneumoconiosis
/
Primary Health Care
/
Talc
/
Bird Fancier's Lung
/
Abdominal Pain
Type of study:
Controlled clinical trial
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Diagnostic study
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Incidence study
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Observational study
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Prognostic study
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Risk factors
Limits:
Humans
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Male
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Animals
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Female
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Adolescent
/
Aged
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Child
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Child, preschool
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Infant
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Infant, Newborn
Country/Region as subject:
Asia
/
Europa
Language:
English
/
Spanish
Journal:
J. physiol. biochem
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An. pediatr. (2003. Ed. impr.)
/
Arch. bronconeumol. (Ed. impr.)
/
Cir. Esp. (Ed. impr.)
/
Nutr. hosp
/
Rev. esp. patol. torac
Year:
2023
/
2022
/
2024
Document type:
Article
Institution/Affiliation country:
Universitat de Barcelona/Spain
/
Affiliated Hospital of Shandong Medical College (Linyi Geriatric Hospital)/Peoples Republic of China
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Centro de Salud Cuzco/España
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Centro de Salud José Ramón Muñoz Fernández/España
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Centro de Salud La Guindalera/España
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Hospital San Pedro/España
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Hospital Universitario Virgen Macarena/España
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The Second Affiliated Hospital of Soochow University/Peoples Republic of China
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Universidad de Murcia/España
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University Hospital of Besancon/France