Refereed journal article or data article (A1)
Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability
List of Authors: Kantonen Tatu, Pekkarinen Laura, Karjalainen Tomi, Bucci Marco, Kalliokoski Kari, Haaparanta-Solin Merja, Aarnio Richard, Dickens Alex M., von Eyken Annie, Laitinen Kirsi, Houttu Noora, Kirjavainen Anna K., Helin Semi, Hirvonen Jussi, Rönnemaa Tapani, Nuutila Pirjo, Nummenmaa Lauri
Publisher: Springer Nature
Publication year: 2022
Journal: International Journal of Obesity
Journal name in source: International Journal of Obesity
Volume number: 46
Start page: 400
End page: 407
eISSN: 1476-5497
DOI: http://dx.doi.org/10.1038/s41366-021-00996-y
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/67757504
Background
Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity.
MethodsSubjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects’ physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2.
ResultsSubjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects).
ConclusionsThese results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.
Downloadable publication This is an electronic reprint of the original article. |