Context In obese individuals, adipocyte endocrine function is affected by altered autophagy. Genetic variants in autophagy-related gene 7 (ATG7) correlated with serum chemerin (RARRES2) concentrations. Objectives 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. Design 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 3T3L1-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 were investigated using a luciferase assay. Setting Mouse model, clinical trials, in vitro studies. Participants Native American (n=83) and Caucasian (n=100) cohort. Main outcome measure Adipocyte chemerin expression and secretion. Results 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 BMI, fat mass (r > 0.27, P < 0.01), and adipocyte cell size (r > 0.42, P < 0.02). Atg7-knockdown in 3T3L1-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). Conclusions 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.
Atg7-knockdown reduces chemerin secretion in murine adipocytes
Piaggi, Paolo;
2019-01-01
Abstract
Context In obese individuals, adipocyte endocrine function is affected by altered autophagy. Genetic variants in autophagy-related gene 7 (ATG7) correlated with serum chemerin (RARRES2) concentrations. Objectives 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. Design 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 3T3L1-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 were investigated using a luciferase assay. Setting Mouse model, clinical trials, in vitro studies. Participants Native American (n=83) and Caucasian (n=100) cohort. Main outcome measure Adipocyte chemerin expression and secretion. Results 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 BMI, fat mass (r > 0.27, P < 0.01), and adipocyte cell size (r > 0.42, P < 0.02). Atg7-knockdown in 3T3L1-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). Conclusions 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
