PMID- 31011777 OWN - NLM STAT- MEDLINE DCOM- 20200113 LR - 20221129 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 62 IP - 6 DP - 2019 Jun TI - Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight. PG - 1048-1064 LID - 10.1007/s00125-019-4866-5 [doi] AB - AIMS/HYPOTHESIS: Obesity and insulin resistance may be associated with altered expression and secretion of adipokines. Physical activity can markedly improve insulin sensitivity, but the association with adipokines remains largely unknown. In this study, we examined the effects of physical activity on the subcutaneous white adipose tissue (scWAT) secretome and its relationship to insulin sensitivity. METHODS: As reported previously, we enrolled 26 sedentary, middle-aged men (13 dysglycaemic and overweight; 13 normoglycaemic and of healthy weight) into a 12 week, supervised, intensive physical exercise intervention that included two endurance and two resistance sessions each week. Insulin sensitivity was measured as the glucose infusion rate from a euglycaemic-hyperinsulinaemic clamp. In our previous study, we measured maximum oxygen uptake, upper- and lower-body strength and a range of circulating biomarkers, and quantified adipose tissue depots using MRI and magnetic resonance spectroscopy. We have now performed global mRNA sequencing, microarrays and RT-PCR of scWAT and skeletal muscle biopsies, and quantified selected plasma adipokines by ELISA. RESULTS: Insulin sensitivity increased similarly in both dysglycaemic (45%) and normoglycaemic (38%) men after 12 weeks of exercise, as reported previously. mRNA sequencing of scWAT revealed 90 transcripts that responded to exercise in dysglycaemic men, whereas only marginal changes were observed in normoglycaemic men. These results were validated using microarrays and RT-PCR. A total of 62 out of 90 transcripts encoded secreted proteins. Overall, 17 transcripts were upregulated and 73 transcripts were downregulated. Downregulated transcripts included several macrophage markers, and were associated with inflammatory and immune-related pathways. Levels of these immune-related transcripts were enhanced in dysglycaemic men vs normoglycaemic men at baseline, but were normalised after the exercise intervention. Principal component and correlation analyses revealed inverse correlations between levels of these immune-related transcripts and insulin sensitivity at baseline, after the intervention, and for the change between baseline and after the intervention. In addition, levels of these transcripts at baseline could predict exercise-induced improvements in insulin sensitivity. Adipokine levels in scWAT (but not in skeletal muscle) were significantly correlated with corresponding plasma adipokine concentrations, as exemplified by leptin, high-molecular-weight adiponectin and secreted frizzled-related protein 4 (SFRP4). SFRP4 mRNA was the most exercise-responsive transcript in scWAT from dysglycaemic men, and plasma SFRP4 concentrations were reduced in dysglycaemic men, but not in normoglycaemic men, after 12 weeks of exercise. CONCLUSIONS/INTERPRETATION: This study indicates that scWAT may be an important mediator of exercise-induced improvements in insulin sensitivity, especially in overweight dysglycaemic individuals at increased risk of developing type 2 diabetes. FAU - Lee, Sindre AU - Lee S AD - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372, Oslo, Norway. sindre.lee@medisin.uio.no. AD - Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. sindre.lee@medisin.uio.no. FAU - Norheim, Frode AU - Norheim F AD - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372, Oslo, Norway. FAU - Langleite, Torgrim M AU - Langleite TM AD - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372, Oslo, Norway. FAU - Gulseth, Hanne L AU - Gulseth HL AD - Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. AD - Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway. FAU - Birkeland, Kare I AU - Birkeland KI AD - Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Drevon, Christian A AU - Drevon CA AD - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372, Oslo, Norway. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190422 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Adipokines) RN - 0 (Blood Glucose) RN - 0 (RNA, Messenger) RN - S88TT14065 (Oxygen) SB - IM EIN - Diabetologia. 2023 Feb;66(2):410. PMID: 36445395 MH - Adipokines/*blood MH - Adipose Tissue, White/metabolism MH - Adult MH - Blood Glucose/metabolism MH - Exercise/*physiology MH - Female MH - Humans MH - Inflammation/*blood MH - Male MH - Middle Aged MH - Overweight/physiopathology MH - Oxygen/metabolism MH - Oxygen Consumption/physiology MH - Principal Component Analysis MH - RNA, Messenger/metabolism MH - Sedentary Behavior MH - Subcutaneous Fat/metabolism OTO - NOTNLM OT - Adipokines OT - Humans OT - Insulin sensitivity OT - Long-term exercise OT - Prediabetes OT - Subcutaneous adipose tissue EDAT- 2019/04/24 06:00 MHDA- 2020/01/14 06:00 CRDT- 2019/04/24 06:00 PHST- 2019/01/11 00:00 [received] PHST- 2019/03/01 00:00 [accepted] PHST- 2019/04/24 06:00 [pubmed] PHST- 2020/01/14 06:00 [medline] PHST- 2019/04/24 06:00 [entrez] AID - 10.1007/s00125-019-4866-5 [pii] AID - 10.1007/s00125-019-4866-5 [doi] PST - ppublish SO - Diabetologia. 2019 Jun;62(6):1048-1064. doi: 10.1007/s00125-019-4866-5. Epub 2019 Apr 22.