Atg7 Knockdown Reduces Chemerin Secretion in Murine Adipocytes.
3T3-L1 Cells
Adipocytes
/ metabolism
Adipose Tissue
/ metabolism
Adiposity
/ physiology
Adult
Aged
Animals
Autophagy-Related Protein 7
/ genetics
Body Mass Index
Chemokines
/ metabolism
Diet
Female
Gene Knockdown Techniques
Humans
Intercellular Signaling Peptides and Proteins
/ metabolism
Male
Mice
Middle Aged
Obesity
/ genetics
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
12
09
2018
accepted:
17
06
2019
pubmed:
22
6
2019
medline:
4
6
2020
entrez:
22
6
2019
Statut:
ppublish
Résumé
In individuals with obesity, adipocyte endocrine function is affected by altered autophagy. Genetic variants in autophagy-related gene 7 (ATG7) correlated with serum chemerin (RARRES2) concentrations. To investigate a functional interplay between chemerin and ATG7, how it may relate to autophagy-mediated adipocyte dysfunction in obesity, and the relevance of genetic ATG7 variants in chemerin physiology. Adipose ATG7 mRNA expression and adiposity measures were available in two human study cohorts. The effect of a high-calorie diet on adipose Rarres2 and Atg7 expression was investigated in mice. In 3T3-L1 adipocytes, the effect of Atg7 knockdown on chemerin expression and secretion was studied. The influence of single nucleotide polymorphisms on ATG7 transcription and chemerin physiology was investigated using a luciferase assay. Mouse model, clinical trials, in vitro studies. Native American (n = 83) and white (n = 100) cohorts. Adipocyte chemerin expression and secretion. In mice fed a high-calorie diet, adipose Atg7 mRNA expression did not parallel an increase in Rarres2 mRNA expression. ATG7 mRNA expression in human subcutaneous adipose tissue correlated with body mass index, fat mass (r > 0.27; P < 0.01), and adipocyte cell size (r > 0.24; P < 0.02). Atg7 knockdown in 3T3-L1 adipocytes decreased chemerin secretion by 22% (P < 0.04). Rs2606729 in ATG7 was predicted to alter ATG7 transcription and induced higher luciferase activity in vitro (P < 0.0001). Human adipose ATG7 mRNA expression relates to measures of adiposity. Atg7 knockdown reduces chemerin secretion from adipocytes in vitro, supportive of a functional interplay between ATG7 and chemerin in autophagy-mediated adipocyte dysfunction.
Identifiants
pubmed: 31225870
pii: 5520798
doi: 10.1210/jc.2018-01980
pmc: PMC7453040
doi:
Substances chimiques
Atg7 protein, mouse
0
Chemokines
0
Intercellular Signaling Peptides and Proteins
0
chemerin protein, mouse
0
Autophagy-Related Protein 7
EC 6.2.1.45
Banques de données
ClinicalTrials.gov
['NCT00340132']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5715-5728Informations de copyright
Copyright © 2019 Endocrine Society.
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