Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects
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Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects. / Sievert, Helen; Krause, Christin; Geißler, Cathleen; Grohs, Martina; El-Gammal, Alexander T; Wolter, Stefan; Mann, Oliver; Lehnert, Hendrik; Kirchner, Henriette.
In: EXP CLIN ENDOCR DIAB, Vol. 129, No. 9, 09.2021, p. 674-682.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects
AU - Sievert, Helen
AU - Krause, Christin
AU - Geißler, Cathleen
AU - Grohs, Martina
AU - El-Gammal, Alexander T
AU - Wolter, Stefan
AU - Mann, Oliver
AU - Lehnert, Hendrik
AU - Kirchner, Henriette
N1 - © Georg Thieme Verlag KG Stuttgart · New York.
PY - 2021/9
Y1 - 2021/9
N2 - OBJECTIVE: The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN (fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits.SUBJECTS AND METHODS: Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing.RESULTS: FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (SCD, ELOVL6) or lipolytic genes (ADRB3, PNPLA2) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = - 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005).CONCLUSIONS: Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.
AB - OBJECTIVE: The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN (fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits.SUBJECTS AND METHODS: Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing.RESULTS: FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (SCD, ELOVL6) or lipolytic genes (ADRB3, PNPLA2) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = - 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005).CONCLUSIONS: Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.
U2 - 10.1055/a-1150-7446
DO - 10.1055/a-1150-7446
M3 - SCORING: Journal article
C2 - 32434239
VL - 129
SP - 674
EP - 682
JO - EXP CLIN ENDOCR DIAB
JF - EXP CLIN ENDOCR DIAB
SN - 0947-7349
IS - 9
ER -