title: Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.
abstract: We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity.
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. Electronic address: m.a.wijngaarden@lumc.nl.
authors.forename: M A
authors.initials: MA
authors.lastname: Wijngaarden
authors.affiliation: Leiden Institute for Brain and Cognition (LIBC), Leiden University, 2300RC Leiden, The Netherlands; Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany. Electronic address: i.m.veer@lumc.nl.
authors.forename: I M
authors.initials: IM
authors.lastname: Veer
authors.affiliation: Leiden Institute for Brain and Cognition (LIBC), Leiden University, 2300RC Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands; Institute of Psychology, Leiden University, 2333 AK Leiden, The Netherlands. Electronic address: s.a.r.b.rombouts@lumc.nl.
authors.forename: S A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: Leiden Institute for Brain and Cognition (LIBC), Leiden University, 2300RC Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. Electronic address: m.a.van_buchem@lumc.nl.
authors.forename: M A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, 2333ZA Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. Electronic address: k.willems_van_dijk@lumc.nl.
authors.forename: K
authors.initials: K
authors.lastname: Willems van Dijk
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. Electronic address: h.pijl@lumc.nl.
authors.forename: H
authors.initials: H
authors.lastname: Pijl
authors.affiliation: Department of Radiology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. Electronic address: j.van_der_grond@lumc.nl.
authors.forename: J
authors.initials: J
authors.lastname: van der Grond
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005215:Fasting / Q000502:physiology*; D005260:Female; D005502:Food; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D012146:Rest; D012201:Reward
keywords: Amygdala; Default-mode network; Fasting; Functional MRI; Hypothalamus; Obesity