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The Insulin Effect on Cerebrocortical Theta Activity Is Associated with Serum Concentrations of Saturated Nonesterified Fatty Acids

Department of Internal Medicine IV (O.T., A.M.H., T.S., Y.G., N.S., M.G., S.D., E.S., A.C., A.F., H.-U.H.), University Hospital, University of Tübingen, 72076 Tübingen, Germany; Institute of Medical Psychology and Behavioral Neurobiology (H.P., N.B.), University of Tübingen, 72076 Tübingen, Germany; Department of Obstetrics and Gynecology (H.P.), College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; Section on Experimental Radiology (J.M.), Department of Diagnostic Radiology, University of Tübingen, 72076 Tübingen, Germany; and Ospedale San Camillo (N.B.), Istituto di Ricovero e Cura a Carattere Scientifico, 30126 Venezia Lido, Italy

Address all correspondence and requests for reprints to: Otto Tschritter, M.D., University of Tübingen, Department of Internal Medicine IV, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. E-mail: otto.tschritter{at}med.uni-tuebingen.de.

Context: Insulin action in the brain contributes to adequate regulation of body weight, neuronal survival, and suppression of endogenous glucose production. We previously demonstrated by magnetoencephalography in lean humans that insulin stimulates activity in beta and theta frequency bands, whereas this effect was abolished in obese individuals.

Objective: The present study aims to define metabolic signals associated with the suppression of the cerebrocortical response in obese humans.

Design and Setting: We determined insulin-mediated modulation of spontaneous cerebrocortical activity by magnetoencephalography during a hyperinsulinemic euglycemic clamp and related it to measures of ectopic fat deposition and mediators of peripheral insulin resistance. Visceral fat mass and intrahepatic lipid content were quantified by magnetic resonance imaging and spectroscopy. Multiple regression analysis was used to analyze associations of cerebrocortical insulin sensitivity and metabolic markers related to obesity.

Participants: Forty-nine healthy, nondiabetic humans participated in the study.

Results: In a multiple regression, insulin-mediated stimulation of theta activity was negatively correlated to body mass index, visceral fat mass, and intrahepatic lipid content. Although fasting saturated nonesterified fatty acids mediated the correlations of theta activity with abdominal and intrahepatic lipid stores, adipocytokines displayed no independent correlation with insulin-mediated cortical activity in the theta frequency band.

Conclusions: Thus, insulin action at the level of cerebrocortical activity in the brain is diminished in the presence of elevated levels of saturated nonesterified fatty acids.