Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
Core Unit DNA Technologies, Medical Faculty, Leipzig University, Leipzig, Germany.
Am J Clin Nutr. 2022 Jul 6;116(1):165-172. doi: 10.1093/ajcn/nqac070.
MicroRNAs (miRNAs) are short noncoding RNAs and important posttranscriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism.
We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity.
This study included adults with abdominal obesity from an 18-mo diet and physical activity intervention trial. Circulating miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 mo; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal adipose tissue [visceral (VAT), deep subcutaneous (DSAT), and superficial subcutaneous (SSAT) adipose tissue; cm2] (n = 144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n = 141) and pancreas (n = 143).
Greater decreases in miR-100-5p were associated with more reductions of VAT (β ± SE per 1-SD decrease: -9.63 ± 3.13 cm2; P = 0.0025), DSAT (β ± SE: -5.48 ± 2.36 cm2; P = 0.0218), SSAT (β ± SE: -4.64 ± 1.68 cm2; P = 0.0067), and intrahepatic fat percentage (β ± SE: -1.54% ± 0.49%; P = 0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-mo reductions of VAT (β ± SE: -10.12 ± 3.31 cm2 per 1-SD decrease; P = 0.0027) and intrahepatic fat percentage (β ± SE: -1.28% ± 0.52%; P = 0.015). Further, decreases in circulating miR-99b-5p (β ± SE: per 1-SD decrease: -0.44% ± 0.21%; P = 0.038) and miR-100-5p (β ± SE: -0.50% ± 0.23%; P = 0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 mo.
Decreases in circulating miR-99-5p/100-5p expression induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity.This trial was registered at clinicaltrials.gov as NCT01530724.
微小 RNA（miRNAs）是短的非编码 RNA，是基因表达的重要转录后调控因子。脂肪组织是循环 miRNA 的主要来源；与脂肪相关的循环 miRNA 可能调节体脂肪分布和葡萄糖代谢。
我们研究了脂肪相关循环 microRNAs-99/100（miR-99/100）对生活方式干预的反应如何与改善体脂肪分布以及减少腹部肥胖成年人的致糖尿病异位脂肪沉积有关。
这项研究包括来自 18 个月饮食和体力活动干预试验的腹部肥胖成年人。在基线和 18 个月时测量循环 miR-99a-5p、miR-99b-5p 和 miR-100-5p；评估这些 miRNA 对干预的反应。主要结果是腹部脂肪组织[内脏（VAT）、深皮下（DSAT）和浅皮下（SSAT）脂肪组织；cm2]的变化（n=144）。次要结果是肝脏（n=141）和胰腺（n=143）异位脂肪堆积的变化。
miR-100-5p 下降幅度越大，VAT（每 1-SD 下降的β±SE：-9.63±3.13 cm2；P=0.0025）、DSAT（β±SE：-5.48±2.36 cm2；P=0.0218）、SSAT（β±SE：-4.64±1.68 cm2；P=0.0067）和肝内脂肪百分比（β±SE：-1.54%±0.49%；P=0.0023）的减少幅度越大。同样，miR-99a-5p 下降幅度较大的参与者，VAT（每 1-SD 下降的β±SE：-10.12±3.31 cm2；P=0.0027）和肝内脂肪百分比（β±SE：-1.28%±0.52%；P=0.015）的 18 个月降低幅度也较大。此外，循环 miR-99b-5p（β±SE：每 1-SD 下降的β±SE：-0.44%±0.21%；P=0.038）和 miR-100-5p（β±SE：-0.50%±0.23%；P=0.033）的降低与胰腺脂肪百分比的降低以及 18 个月时葡萄糖代谢和胰岛素分泌的改善有关。
生活方式干预诱导的循环 miR-99-5p/100-5p 表达下降与改善体脂肪分布和异位脂肪堆积有关。我们的研究表明，腹部肥胖患者循环脂肪相关 miR-99-5p/100-5p 的变化可能与减少致糖尿病脂肪沉积有关。这项试验在 clinicaltrials.gov 上注册为 NCT01530724。
