Jaakko Hentilä, Jouni Tuisku, Ronja Ojala, Lihua Sun, Martin S Lietzén, Heidi Virtanen, Riikka Lautamäki, Kalle Koskensalo, Lauri Nummenmaa, Eliisa Löyttyniemi, Semi Helin, Kirsi H Pietiläinen, Jaakko Kaprio, Leo Lahti, Tarja Malm, Juha O Rinne, Jarna C Hannukainen
{"title":"肥胖与脑葡萄糖摄取和活动增加有关，但与bmi不一致的同卵双胞胎的神经炎症（TSPO可用性）无关——运动训练逆转脑活动增加。","authors":"Jaakko Hentilä, Jouni Tuisku, Ronja Ojala, Lihua Sun, Martin S Lietzén, Heidi Virtanen, Riikka Lautamäki, Kalle Koskensalo, Lauri Nummenmaa, Eliisa Löyttyniemi, Semi Helin, Kirsi H Pietiläinen, Jaakko Kaprio, Leo Lahti, Tarja Malm, Juha O Rinne, Jarna C Hannukainen","doi":"10.1111/dom.70109","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Obesity is associated with increased insulin-stimulated brain glucose uptake (BGU) which is opposite to decreased GU observed in peripheral tissues. Increased BGU was shown to be reversed by weight loss and exercise training, but the mechanisms remain unknown. We investigated whether neuroinflammation (TSPO availability) and brain activity drive the obesity-associated increase in BGU and whether this increase is reversed by exercise training.</p><p><strong>Materials and methods: </strong>Twelve monozygotic twin pairs mean age 40.4 (SD) years discordant for BMI (leaner mean 29.1 (SD) 6.3, heavier 36.7 (SD) 7.0 kg·m<sup>-2</sup>) performed 6-month long exercise intervention. Insulin-stimulated BGU during euglycaemic-hyperinsulinaemic clamp, brain inflammation (translocator protein (TSPO) availability) and brain resting state activity were studied by [<sup>18</sup>F]FDG-PET, [<sup>11</sup>C]PK11195-PET, and fMRI, respectively. Cognitive function was assessed by an online survey.</p><p><strong>Results: </strong>Exercise training had no effect on insulin-stimulated BGU, brain neuroinflammation (TSPO availability), or BMI. Exercise improved VO<sub>2peak</sub>, whole-body insulin sensitivity, and cognitive function similarly in both groups (all, p <0.05) as well as decreased resting state brain activity in heavier co-twins (p <0.05). At baseline, heavier co-twins had worse whole-body insulin sensitivity (p <0.01), increased BGU in the parietal cortex and caudatus, as well as increased resting state brain activity (both, p <0.05) and no difference in cognitive function. Leaner co-twins had higher TSPO availability in white matter and the hippocampus (p <0.05).</p><p><strong>Conclusions: </strong>Exercise training had no effect on insulin-stimulated BGU or neuroinflammation (TSPO availability) but it reversed increased resting state brain activity in heavier co-twins. At baseline, obesity was associated with increased insulin-stimulated BGU and resting state brain activity, independent of genetics.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Obesity is associated with increased brain glucose uptake and activity but not neuroinflammation (TSPO availability) in monozygotic twin pairs discordant for BMI-Exercise training reverses increased brain activity.\",\"authors\":\"Jaakko Hentilä, Jouni Tuisku, Ronja Ojala, Lihua Sun, Martin S Lietzén, Heidi Virtanen, Riikka Lautamäki, Kalle Koskensalo, Lauri Nummenmaa, Eliisa Löyttyniemi, Semi Helin, Kirsi H Pietiläinen, Jaakko Kaprio, Leo Lahti, Tarja Malm, Juha O Rinne, Jarna C Hannukainen\",\"doi\":\"10.1111/dom.70109\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Obesity is associated with increased insulin-stimulated brain glucose uptake (BGU) which is opposite to decreased GU observed in peripheral tissues. Increased BGU was shown to be reversed by weight loss and exercise training, but the mechanisms remain unknown. We investigated whether neuroinflammation (TSPO availability) and brain activity drive the obesity-associated increase in BGU and whether this increase is reversed by exercise training.</p><p><strong>Materials and methods: </strong>Twelve monozygotic twin pairs mean age 40.4 (SD) years discordant for BMI (leaner mean 29.1 (SD) 6.3, heavier 36.7 (SD) 7.0 kg·m<sup>-2</sup>) performed 6-month long exercise intervention. Insulin-stimulated BGU during euglycaemic-hyperinsulinaemic clamp, brain inflammation (translocator protein (TSPO) availability) and brain resting state activity were studied by [<sup>18</sup>F]FDG-PET, [<sup>11</sup>C]PK11195-PET, and fMRI, respectively. Cognitive function was assessed by an online survey.</p><p><strong>Results: </strong>Exercise training had no effect on insulin-stimulated BGU, brain neuroinflammation (TSPO availability), or BMI. Exercise improved VO<sub>2peak</sub>, whole-body insulin sensitivity, and cognitive function similarly in both groups (all, p <0.05) as well as decreased resting state brain activity in heavier co-twins (p <0.05). At baseline, heavier co-twins had worse whole-body insulin sensitivity (p <0.01), increased BGU in the parietal cortex and caudatus, as well as increased resting state brain activity (both, p <0.05) and no difference in cognitive function. Leaner co-twins had higher TSPO availability in white matter and the hippocampus (p <0.05).</p><p><strong>Conclusions: </strong>Exercise training had no effect on insulin-stimulated BGU or neuroinflammation (TSPO availability) but it reversed increased resting state brain activity in heavier co-twins. At baseline, obesity was associated with increased insulin-stimulated BGU and resting state brain activity, independent of genetics.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.70109\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.70109","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Obesity is associated with increased brain glucose uptake and activity but not neuroinflammation (TSPO availability) in monozygotic twin pairs discordant for BMI-Exercise training reverses increased brain activity.
Aims: Obesity is associated with increased insulin-stimulated brain glucose uptake (BGU) which is opposite to decreased GU observed in peripheral tissues. Increased BGU was shown to be reversed by weight loss and exercise training, but the mechanisms remain unknown. We investigated whether neuroinflammation (TSPO availability) and brain activity drive the obesity-associated increase in BGU and whether this increase is reversed by exercise training.
Materials and methods: Twelve monozygotic twin pairs mean age 40.4 (SD) years discordant for BMI (leaner mean 29.1 (SD) 6.3, heavier 36.7 (SD) 7.0 kg·m-2) performed 6-month long exercise intervention. Insulin-stimulated BGU during euglycaemic-hyperinsulinaemic clamp, brain inflammation (translocator protein (TSPO) availability) and brain resting state activity were studied by [18F]FDG-PET, [11C]PK11195-PET, and fMRI, respectively. Cognitive function was assessed by an online survey.
Results: Exercise training had no effect on insulin-stimulated BGU, brain neuroinflammation (TSPO availability), or BMI. Exercise improved VO2peak, whole-body insulin sensitivity, and cognitive function similarly in both groups (all, p <0.05) as well as decreased resting state brain activity in heavier co-twins (p <0.05). At baseline, heavier co-twins had worse whole-body insulin sensitivity (p <0.01), increased BGU in the parietal cortex and caudatus, as well as increased resting state brain activity (both, p <0.05) and no difference in cognitive function. Leaner co-twins had higher TSPO availability in white matter and the hippocampus (p <0.05).
Conclusions: Exercise training had no effect on insulin-stimulated BGU or neuroinflammation (TSPO availability) but it reversed increased resting state brain activity in heavier co-twins. At baseline, obesity was associated with increased insulin-stimulated BGU and resting state brain activity, independent of genetics.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
