PMID- 34728775
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20221028
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Print)
IS  - 0307-0565 (Linking)
VI  - 46
IP  - 2
DP  - 2022 Feb
TI  - Obesity risk is associated with altered cerebral glucose metabolism and decreased 
      mu-opioid and CB(1) receptor availability.
PG  - 400-407
LID - 10.1038/s41366-021-00996-y [doi]
AB  - 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, mu-opioid receptors (MORs) and 
      cannabinoid CB(1) receptors (CB(1)Rs) are associated with risk for developing 
      obesity. METHODS: Subjects 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 [(18)F]FDG during hyperinsulinemic 
      euglycemic clamp, MORs were quantified with [(11)C]carfentanil and CB(1)Rs with 
      [(18)F]FMPEP-d(2). RESULTS: Subjects 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 CB(1)Rs (36 subjects). CONCLUSIONS: These results suggest that 
      the hereditary mechanisms promoting obesity may be partly mediated via insulin, 
      opioid and endocannabinoid messaging systems in the brain.
CI  - (c) 2021. The Author(s).
FAU - Kantonen, Tatu
AU  - Kantonen T
AUID- ORCID: 0000-0002-2336-0426
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland. taskan@utu.fi.
AD  - Clinical Neurosciences, Turku University Hospital, Turku, FI-20521, Finland. 
      taskan@utu.fi.
FAU - Pekkarinen, Laura
AU  - Pekkarinen L
AUID- ORCID: 0000-0002-5596-0485
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Department of Endocrinology, Turku University Hospital, Turku, FI-20521, Finland.
FAU - Karjalainen, Tomi
AU  - Karjalainen T
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Turku PET Centre, Turku University Hospital, Turku, FI-20521, Finland.
FAU - Bucci, Marco
AU  - Bucci M
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Turku PET Centre, Abo Akademi University, Turku, FI-20500, Finland.
FAU - Kalliokoski, Kari
AU  - Kalliokoski K
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
FAU - Haaparanta-Solin, Merja
AU  - Haaparanta-Solin M
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - MediCity Research Laboratory, University of Turku, Turku, FI-20500, Finland.
FAU - Aarnio, Richard
AU  - Aarnio R
AUID- ORCID: 0000-0002-6420-514X
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
FAU - Dickens, Alex M
AU  - Dickens AM
AD  - Turku Bioscience Centre, University of Turku and Abo Akademi University, Turku, 
      FI-20500, Finland.
FAU - von Eyken, Annie
AU  - von Eyken A
AD  - Turku Bioscience Centre, University of Turku and Abo Akademi University, Turku, 
      FI-20500, Finland.
FAU - Laitinen, Kirsi
AU  - Laitinen K
AUID- ORCID: 0000-0001-5245-8118
AD  - Institute of Biomedicine, Research Centre for Integrative Physiology and 
      Pharmacology, University of Turku, Turku, FI-20500, Finland.
FAU - Houttu, Noora
AU  - Houttu N
AD  - Institute of Biomedicine, Research Centre for Integrative Physiology and 
      Pharmacology, University of Turku, Turku, FI-20500, Finland.
FAU - Kirjavainen, Anna K
AU  - Kirjavainen AK
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
FAU - Helin, Semi
AU  - Helin S
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
FAU - Hirvonen, Jussi
AU  - Hirvonen J
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Department of Radiology, University of Turku and Turku University Hospital, 
      Turku, FI-20500, Finland.
FAU - Ronnemaa, Tapani
AU  - Ronnemaa T
AD  - Department of Endocrinology, Turku University Hospital, Turku, FI-20521, Finland.
AD  - Department of Medicine, University of Turku, Turku, FI-20500, Finland.
FAU - Nuutila, Pirjo
AU  - Nuutila P
AUID- ORCID: 0000-0001-9597-338X
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Department of Endocrinology, Turku University Hospital, Turku, FI-20521, Finland.
FAU - Nummenmaa, Lauri
AU  - Nummenmaa L
AD  - Turku PET Centre, University of Turku, Turku, FI-20521, Finland.
AD  - Department of Psychology, University of Turku, Turku, FI-20500, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211102
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, Opioid, mu)
SB  - IM
MH  - Adult
MH  - Body Mass Index
MH  - Cerebrum/*metabolism/physiopathology
MH  - Female
MH  - Finland/epidemiology
MH  - Glucose Intolerance/epidemiology/*etiology/metabolism
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Obesity/*diagnosis/epidemiology/metabolism
MH  - Positron-Emission Tomography/methods/statistics & numerical data
MH  - Receptor, Cannabinoid, CB1/*drug effects/metabolism
MH  - Receptors, Opioid, mu/*drug effects/metabolism
MH  - Risk Factors
PMC - PMC8794779
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/04 06:00
MHDA- 2022/02/19 06:00
PMCR- 2021/11/02
CRDT- 2021/11/03 06:47
PHST- 2020/12/10 00:00 [received]
PHST- 2021/10/12 00:00 [accepted]
PHST- 2021/07/06 00:00 [revised]
PHST- 2021/11/04 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/11/03 06:47 [entrez]
PHST- 2021/11/02 00:00 [pmc-release]
AID - 10.1038/s41366-021-00996-y [pii]
AID - 996 [pii]
AID - 10.1038/s41366-021-00996-y [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2022 Feb;46(2):400-407. doi: 10.1038/s41366-021-00996-y. Epub 
      2021 Nov 2.