Endogenous GLP‐1 alters postprandial functional connectivity between homeostatic and reward‐related brain regions involved in regulation of appetite in healthy lean males: A pilotstudy

摘要

Aims Peripheral infusion of glucagon‐like peptide‐1 (GLP‐1) can affect brain activity in areas involved in the regulation of appetite, including hypothalamic and reward‐related brain regions. In contrast, the physiological role of endogenous GLP‐1 in the central regulation of appetite has hardly been investigated. Materials and Methods This was a randomized, cross‐over trial that involved 12 healthy volunteers who received an intragastric (ig) glucose (gluc) load, with or without intravenous (iv) exendin9‐39 (ex9‐39; specific GLP‐1 receptor antagonist). Functional magnetic resonance imaging was used to investigate the effect of endogenous GLP‐1 on resting state functional connectivity (rsFC) between homeostatic and reward‐related brain regions. Visual analogue scales were used to rate appetite‐related sensations. Blood samples were collected for GI hormone measurements. Results Administration of iv‐ex9‐39/ig‐gluc induced a significantly higher rsFC, relative to ig‐gluc administration, between the hypothalamus and the left lateral orbitofrontal cortex (OFC) as well as the left amygdala ( P ≤ .001, respectively). Administration of iv‐ex9‐39/ig‐gluc induced a significantly higher rsFC, relative to ig‐gluc administration, between the right nucleus accumbens and the right lateral OFC ( P .001). Administration of iv‐ex9‐39/ig‐gluc induced a significantly lower rsFC, relative to ig‐gluc administration, between the midbrain and the right caudate nucleus ( P = .001). Administration of ig‐gluc significantly decreased prospective food consumption and increased sensations of fullness compared to pre‐infusion baseline ( P = .028 and P = .019, respectively); these effects were not present in the iv‐ex9‐39/ig‐gluc condition. Conclusions This pilot trial provides preliminary experimental evidence that glucose‐induced endogenous GLP‐1 affects central regulation of appetite by modulating rsFC in homeostatic and reward‐related brain regions in healthy lean male participants in a GLP‐1 receptor‐mediated fashion.