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A polygenic risk score of lipolysis-increasing alleles determines visceral fat mass and proinsulin conversion.

J. Clin. Endocrinol. Metab. 104, 1090-1098 (2019)
Publishers Version online available 03/2020 Free by publisher Postprint online available 03/2020 Open Access Green as soon as is submitted to ZB.
CONTEXT: Primary dysregulation of adipose tissue lipolysis caused by genetic variation and independent of insulin resistance could explain unhealthy body fat distribution and its metabolic consequences. OBJECTIVE: To analyze common single nucleotide polymorphisms (SNPs) in 48 lipolysis-, but not insulin-signaling-related genes, to form polygenic risk scores of lipolysis-associated SNPs, and to investigate their effects on body fat distribution, glycemia, insulin sensitivity, insulin secretion, and proinsulin conversion. STUDY DESIGN, PARTICIPANTS, AND METHODS: SNP array, anthropometric, and metabolic data were available from up to 2789 participants without diabetes of the Tübingen Family study of type 2 diabetes characterized by oral glucose tolerance tests. In a subgroup (n = 942), magnetic resonance measurements of body fat stores were available. RESULTS: We identified insulin-sensitivity-independent nominal associations (P < 0.05) of SNPs in 10 genes with plasma free fatty acids (FFAs), in 7 genes with plasma glycerol and in 6 genes with both, plasma FFAs and glycerol. A score formed of the latter SNPs (in ADCY4, CIDEA, GNAS, PDE8B, PRKAA1, PRKAG2) was associated with plasma FFA and glycerol measurements (1.4*10-9 ≤ P ≤ 1.2*10-5), visceral adipose tissue mass (P = 0.0326), and proinsulin conversion (P ≤ 0.0272). The more lipolysis-increasing alleles a subject had, the lower was the visceral fat mass and the lower the proinsulin conversion. CONCLUSIONS: We found evidence for a genetic basis of adipose tissue lipolysis resulting from common SNPs in CIDEA, AMP-activated protein kinase subunits, and cAMP signaling components. A genetic score of lipolysis-increasing alleles determined lower visceral fat mass and lower proinsulin conversion.
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Publication type Article: Journal article
Document type Scientific Article
Reviewing status