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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\u2010associated increase in BGU and whether this increase is reversed by exercise training.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      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\u2009kg\u00b7m\n                      <jats:sup>\u22122<\/jats:sup>\n                      ) performed 6\u2010month long exercise intervention. Insulin\u2010stimulated BGU during euglycaemic\u2010hyperinsulinaemic clamp, brain inflammation (translocator protein (TSPO) availability) and brain resting state activity were studied by [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG\u2010PET, [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195\u2010PET, and fMRI, respectively. Cognitive function was assessed by an online survey.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exercise training had no effect on insulin\u2010stimulated BGU, brain neuroinflammation (TSPO availability), or BMI. Exercise improved VO\n                      <jats:sub>2peak<\/jats:sub>\n                      , whole\u2010body insulin sensitivity, and cognitive function similarly in both groups (all,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05) as well as decreased resting state brain activity in heavier co\u2010twins (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05). At baseline, heavier co\u2010twins had worse whole\u2010body insulin sensitivity (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), increased BGU in the parietal cortex and caudatus, as well as increased resting state brain activity (both,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05) and no difference in cognitive function. Leaner co\u2010twins had higher TSPO availability in white matter and the hippocampus (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Exercise training had no effect on insulin\u2010stimulated BGU or neuroinflammation (TSPO availability) but it reversed increased resting state brain activity in heavier co\u2010twins. At baseline, obesity was associated with increased insulin\u2010stimulated BGU and resting state brain activity, independent of genetics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70109","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T08:26:45Z","timestamp":1757492805000},"page":"7097-7109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Obesity is associated with increased brain glucose uptake and activity but not neuroinflammation (\n                    <scp>TSPO<\/scp>\n                    availability) in monozygotic twin pairs discordant for\n                    <scp>BMI<\/scp>\n                    \u2014Exercise training reverses increased brain activity"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-8827","authenticated-orcid":false,"given":"Jaakko","family":"Hentil\u00e4","sequence":"first","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jouni","family":"Tuisku","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"},{"name":"Turku PET Centre, Turku University Hospital  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-0281","authenticated-orcid":false,"given":"Ronja","family":"Ojala","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Sun","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"},{"name":"Huashan Institute of Medicine, Huashan Hospital, Fudan University  Shanghai China"},{"name":"Turku Collegium for Science, Medicine and Technology University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin S.","family":"Lietz\u00e9n","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Virtanen","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riikka","family":"Lautam\u00e4ki","sequence":"additional","affiliation":[{"name":"Heart Centre, Turku University Hospital  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalle","family":"Koskensalo","sequence":"additional","affiliation":[{"name":"Department of Medical Physics Turku University Hospital  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauri","family":"Nummenmaa","sequence":"additional","affiliation":[{"name":"Turku PET Centre, University of Turku  Turku Finland"},{"name":"Department of Psychology University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliisa","family":"L\u00f6yttyniemi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semi","family":"Helin","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Chemistry Laboratory, Turku PET Centre University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsi H.","family":"Pietil\u00e4inen","sequence":"additional","affiliation":[{"name":"Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Abdominal Center, Obesity Center, Endocrinology University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaakko","family":"Kaprio","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Lahti","sequence":"additional","affiliation":[{"name":"Department of Computing University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarja","family":"Malm","sequence":"additional","affiliation":[{"name":"A.I. 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