Altered Brain Resting-State Functional Connectivity in Obese Patients Is Associated with Plasma Levels of Leptin

There is growing evidence for the role of the insular cortex in various types of cravings, including food craving. Here, we used resting-state functional brain connectivity (FBC) to explore system-level dysfunctions in the brain of obese (OB) individuals and their correlations with the leptin levels. We first used hierarchical clustering to identify the brain regions whose altered functioning was consistently reported by neuroimaging studies on food perception in OB subjects. We found that a cluster centred in left anterior insula and overlying frontal operculum (AI/fO) was specifically associated with hyper-responsivity in OB. This cluster was then used as a seed for a seed-based FBC analysis in 10 OB and 11 normal weight controls matched for sex, age and education. The analysis implied the calculation of the functional correlations of each brain voxel with the seed along the resting state fMRI time series. OB patients, compared to the control group, showed hyper-connectivity between the left AI/fO and key regions of the reward system, such as the left medial orbitofrontal cortex (OFC), in addition to the bilateral parahippocampal gyri and the posterior cingulate gyrus; conversely, they exhibited hypo-connectivity between the seed and the left dorsolateral prefrontal cortex, a key region involved in inhibitory control (all Ps Disclosure F. Devoto: None. A. Ferrulli: None. L. Zapparoli: None. R. Bonandrini: None. L. Sconfienza: None. G. Banfi: None. L. Luzi: Speaker9s Bureau; Self; A. Menarini Diagnostics, AstraZeneca, Eli Lilly and Company. Research Support; Self; Gelesis. Consultant; Self; McKinsey & Company. Speaker9s Bureau; Self; Menarini Group, Merck Sharp & Dohme Corp.. Research Support; Self; Novartis AG. Speaker9s Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sunstar Foundation. Speaker9s Bureau; Self; Smith & Nephew. E. Paulesu: None.