Lipid laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
Institute of Health and Wellbeing, University of Glasgow, College of Medicine, Veterinarian and Life Sciences, G12 8RZ Glasgow, UK.
Cells. 2020 Apr 27;9(5):1085. doi: 10.3390/cells9051085.
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 , ARHGEF10, , and in adipose morphology by their impact on adipogenesis.
与脂肪沉积大小相比，脂肪细胞大小增加，也称为肥大性脂肪形态，是未来发生胰岛素抵抗和 2 型糖尿病的一个强危险因素。脂肪形态的调节知之甚少。我们着手确定与脂肪形态相关的遗传位点，并对候选基因进行功能评估，以确定其对脂肪细胞发育的影响。我们在独特的脂肪细胞脂解遗传学 (GENiAL) 队列中进行了全基因组关联研究 (GWAS)，该队列包括 948 名参与者，他们接受了腹部皮下脂肪活检，并确定了平均脂肪体积和形态。GWAS 确定了 31 个与脂肪形态呈提示性关联的遗传位点。通过脂肪源性前体细胞中的小干扰 RNA (siRNA)介导的敲低对候选基因进行功能评估，确定了控制脂肪细胞更新和分化的 6 个基因，因此对脂肪肥大具有潜在的重要性。总之，遗传和功能研究表明， 通过对脂肪发生的影响， 在脂肪形态中发挥调节作用。
