TY - JOUR
T1 - Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity
T2 - A combined neuroimaging study
AU - Rebelos, Eleni
AU - Latva-Rasku, Aino
AU - Koskensalo, Kalle
AU - Pekkarinen, Laura
AU - Saukko, Ekaterina
AU - Ihalainen, Jukka
AU - Honka, Miikka-Juhani
AU - Tuisku, Jouni
AU - Bucci, Marco
AU - Laurila, Sanna
AU - Rajander, Johan
AU - Salminen, Paulina
AU - Nummenmaa, Lauri
AU - Jansen, Jacobus Fa
AU - Ferrannini, Ele
AU - Nuutila, Pirjo
PY - 2024/3
Y1 - 2024/3
N2 - The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy ( H-MRS, 3?T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with F-fluorodeoxyglucose positron emission tomography ( F-FDG-PET)) was also performed in a subset of subjects during clamp. In 48 participants were studied during fasting with brain H-MRS, while in 21 participants underwent paired brain H-MRS acquisitions under fasting and clamp conditions. In 16 subjects underwent brain F-FDG-PET and H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.
AB - The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy ( H-MRS, 3?T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with F-fluorodeoxyglucose positron emission tomography ( F-FDG-PET)) was also performed in a subset of subjects during clamp. In 48 participants were studied during fasting with brain H-MRS, while in 21 participants underwent paired brain H-MRS acquisitions under fasting and clamp conditions. In 16 subjects underwent brain F-FDG-PET and H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.
KW - N-acetyl-aspartate
KW - Positron emission tomography
KW - insulin resistance
KW - magnetic resonance spectroscopy
KW - myo-inositol
KW - obesity
U2 - 10.1177/0271678X231207114
DO - 10.1177/0271678X231207114
M3 - Article
SN - 0271-678X
VL - 44
SP - 407
EP - 418
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -