Yoriko Heianza1, Knut Krohn2, Qiaochu Xue1, Anat Yaskolka Meir3, Stefanie Ziesche4, Uta Ceglarek5, Matthias Blüher4,6, Maria Keller4,6, Peter Kovacs4, Iris Shai3,7, Lu Qi1,7. 1. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. 2. Core Unit DNA Technologies, Medical Faculty, Leipzig University, Leipzig, Germany. 3. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 4. Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany. 5. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, Leipzig, Germany. 6. Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich, University of Leipzig and University Hospital Leipzig, Leipzig, Germany. 7. Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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