Affiliation:
1. Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences, East China Normal University Shanghai China
2. Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China
3. Department of Endocrine and Metabolic Diseases The First Affiliated Hospital of Wenzhou Medical University Wenzhou China
Abstract
AbstractAimIron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.MethodsTo investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.ResultsTFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.ConclusionsReduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Chongqing Municipality
National Key Research and Development Program of China
Science and Technology Commission of Shanghai Municipality
Subject
Endocrinology, Diabetes and Metabolism
Cited by
1 articles.
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