Transcriptome analysis of browning human neck area adipocytes reveals strong influence by the FTO intronic SNP variant in addition to tissue and PPARγ specific regulation
Transcriptome analysis of browning human neck area adipocytes reveals strong influence by the FTO intronic SNP variant in addition to tissue and PPARγ specific regulation
Abstract ObjectiveBrown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. Although analyses of tissue samples and cell clones provided important findings, their molecular features are not fully understood. FTO pro-obesity rs1421085 T-to-C SNP shifts differentiation program towards white adipocytes in subcutaneous fat. MethodsHuman adipose-derived stromal cells were obtained from subcutaneous neck (SC) and DN fat of 9 donors, of which 3-3 carried risk-free (T/T), heterozygous or obesity-risk (C/C) FTO genotypes. They were differentiated to white and brown (long-term PPARγ stimulation) adipocytes, then global RNA sequencing was performed and differentially expressed genes (DEGs) were compared. ResultsDN and SC progenitors had similar adipocyte differentiation potential but differed in DEGs. DN adipocytes displayed higher browning features according to ProFAT or BATLAS scores and characteristic DEG patterns revealing associated pathways which were highly expressed (thermogenesis, interferon, cytokine, retinoic acid, with UCP1 and BMP4 as prominent network stabilizers) or downregulated (particularly extracellular matrix remodeling) compared to SC ones. Part of DEGs in either DN or SC browning was PPARγ-dependent determining enrichment for lipid metabolism and induction of some browning genes such as PCK1, CPT1B, and PLIN5. Presence of the FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes with a striking resemblance between affected pathways and those appearing in ProFAT and BATLAS, underlining the importance of metabolic and mitochondrial pathways in thermogenesis. ConclusionsAmong overlapping regulatory influences which determine browning and thermogenic potential of neck adipocytes FTO genetic background has a so far not recognized prominence.
F¨|s¨1s L¨￠szl¨?、Arianti Rini、Bacso Zsolt、Ver¨|b Zolt¨￠n、Shaw Abhirup、Gy?ry Ferenc、Krist¨?f Endre、T¨?th Be¨￠ta B.、P¨?liska Szil¨￠rd、V¨￠mos Attila
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen||Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, DebrecenDepartment of Biophysics and Cell Biology, Faculties of Medicine and Pharmacology, University of DebrecenRegenerative Medicine and Cellular Pharmacology Research Laboratory, Department of Dermatology and Allergology, University of SzegedDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen||Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, DebrecenDepartment of Surgery, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen||Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen
基础医学分子生物学生理学
adipocyte browningdifferential gene expression patternsdeep-neckPPARγFTO obesity-risk allele
F¨|s¨1s L¨￠szl¨?,Arianti Rini,Bacso Zsolt,Ver¨|b Zolt¨￠n,Shaw Abhirup,Gy?ry Ferenc,Krist¨?f Endre,T¨?th Be¨￠ta B.,P¨?liska Szil¨￠rd,V¨￠mos Attila.Transcriptome analysis of browning human neck area adipocytes reveals strong influence by the FTO intronic SNP variant in addition to tissue and PPARγ specific regulation[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/2020.02.21.959593.点此复制
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