Key result
A genome-wide association study identified 31 genetic loci associated with adipose morphology, and functional evaluation implicated 6 genes in adipocyte renewal and differentiation.
Why the study?
Hypertrophic adipose morphology is a strong risk factor for insulin resistance and type 2 diabetes, but the regulation of adipose morphology is poorly understood.
Cohort (n=948)
Genetic and functional studies identified six genes (ATL2, ARHGEF10, CYP1B1, TMEM200A, C17orf51, and L3MBTL3) that play a regulatory role in adipose morphology through their impact on adipogenesis.
These loci are hypothesis-generating for adipose regulation; leaves open any role in cardiometabolic risk prediction or therapy.
An increased adipocyte size relative to the size of fat depots, also denoted hypertrophic adipose morphology, is a strong risk factor for the future development of insulin resistance and type 2 diabetes. The regulation of adipose morphology is poorly understood. We set out to identify genetic loci associated with adipose morphology and functionally evaluate candidate genes for impact on adipocyte development. We performed a genome-wide association study (GWAS) in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort comprising 948 participants who have undergone abdominal subcutaneous adipose biopsy with a determination of average adipose volume and morphology. The GWAS identified 31 genetic loci displaying suggestive association with adipose morphology. Functional evaluation of candidate genes by small interfering RNAs (siRNA)-mediated knockdown in adipose-derived precursor cells identified six genes controlling adipocyte renewal and differentiation, and thus of potential importance for adipose hypertrophy. In conclusion, genetic and functional studies implicate a regulatory role for ATL2, ARHGEF10, CYP1B1, TMEM200A, C17orf51, and L3MBTL3 in adipose morphology by their impact on adipogenesis.
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Lundbäck et al. (2020) conducted a cohort in Hypertrophic adipose morphology (n=948). Genetic loci was evaluated on Adipose morphology. A genome-wide association study identified 31 genetic loci associated with adipose morphology, and functional evaluation implicated 6 genes in adipocyte renewal and differentiation.
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