Elevated insulin levels are often observed in obesity, but the effects of hyperinsulinemia on cerebral blood flow (CBF) are not known. While insulin acts as a satiety factor in lean humans, it is unclear if this CNS effect is maintained in the setting of hyperinsulinemia in obesity. This study aimed to isolate the effects of elevated insulin levels during euglycemia in lean (LN: n=6, BMI 21.1 kg/m2, age 32 years) and obese (OB: n=8, BMI 32, age 30) humans. Participants underwent a 2 hour oral glucose tolerance test [mean 120-min insulin LN 41 mU/ml vs. OB 113 mU/mL (p=.49) and glucose LN 101 mg/dL vs. OB 112 mg/dL (p=.72)] and on 2 separate days received either a saline infusion (control) or underwent a euglycemic-hyperinsulinemic clamp (insulin 2 mU/kg/min, glucose 90 mg/dL) during functional magnetic resonance imaging (fMRI). Whole-brain analyses comparing neural responses on hyperinsulinemic vs. saline control days demonstrated increased CBF in the putamen, insula, anterior cingulate cortex, and middle temporal gyrus in the OB group, but not in the LN group (p=.01, whole-brain corrected; Figure). We conclude that obesity invokes different CBF responses to hyperinsulinemia, specifically in regions implicated in impulsivity, reward processing, and interoceptive signaling. Thus, while in lean humans increased insulin levels signal satiety and reduce food-seeking behavior, this may not be the case in obese humans.

D. Groskreutz: None. R. Sinha: None. C. Lacadie: None. W. Lam: None. M. Hamza: None. C.P. Schmidt: None. D. Seo: None. J. Hwang: None. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc.. J. Leventhal: None. S. Rosenberg: None. L. Parikh: None. T. Constable: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. A.M. Jastreboff: Consultant; Self; Novo Nordisk Inc., Rhythm Pharmaceuticals Inc., Medtronic.

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