Key result
The FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes in human neck adipocytes.
Why the study?
Brown adipocytes in the human deep-neck area have anti-obesity thermogenic potential, and the FTO rs1421085 obesity-risk SNP shifts differentiation toward white adipocytes in subcutaneous fat.
The FTO obesity-risk allele strongly suppresses thermogenic and mitochondrial gene expression in human neck adipocytes, highlighting its role in determining browning potential.
FTO effects on neck adipocyte browning remain hypothesis-generating; leaves open human translation and therapeutic targeting in obesity.
Brown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. FTO pro-obesity rs1421085 T-to-C SNP shifts differentiation program towards white adipocytes in subcutaneous fat. Human 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. DN 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 remodelling) compared to SC ones. Part of DEGs in either DN or SC browning was PPARγ-dependent. 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. Among overlapping regulatory influences which determine browning and thermogenic potential of neck adipocytes, FTO genetic background has a so far not recognized prominence.
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Tóth et al. (2020) studied this question. FTO obesity-risk allele (rs1421085) vs. Risk-free (T/T) FTO genotype was evaluated on Differentially expressed genes (DEGs) and browning features. The FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes in human neck adipocytes.
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