Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis

Abstract

Background/Objectives:The salience network (SN) comprises brain regions that evaluate cues in the external environment in light of internal signals. We examined the SN response to meal intake and potential genetic and acquired influences on SN function.Subjects/Methods:Monozygotic (MZ; 40 pairs) and dizygotic (15 pairs) twins had body composition and plasma metabolic profile evaluated (glucose, insulin, leptin, ghrelin and GLP-1). Twins underwent resting-state functional magnetic resonance imaging (fMRI) scans before and after a standardized meal. The strength of SN connectivity was analyzed pre- and post-meal and the percentage change elicited by a meal was calculated. A multi-echo T2 MRI scan measured T2 relaxation time, a radiologic index of gliosis, in the mediobasal hypothalamus (MBH) and control regions. Statistical approaches included intraclass correlations (ICC) to investigate genetic influences and within-pair analyses to exclude genetic confounders.Results:SN connectivity was reduced by meal ingestion (β=−0.20; P<0.001). Inherited influences on both pre- and post-meal connectivity were present (ICC MZ twins 26%, P<0.05 and 47%, P<0.001, respectively), but not percentage change in response to the meal. SN connectivity in response to a meal did not differ between participants with obesity and of normal weight (χ2(1)=0.93; P=0.33). However, when participants were classified as having high or low signs of MBH gliosis, the high MBH gliosis group failed to reduce the connectivity in response to a meal (z=−1.32; P=0.19). Excluding genetic confounders, the percentage change in SN connectivity by a meal correlated to body fat percentage (r=0.24; P<0.01).Conclusions:SN connectivity was reduced by a meal, indicating potential participation of the SN in control of feeding. The strength of SN connectivity is inherited, but the degree to which SN connectivity is reduced by eating appears to be influenced by adiposity and the presence of hypothalamic gliosis.

Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients

“…In the present study, we asked whether RYGB attenuates obesity-associated hypothalamic inflammation in humans using established radiologic techniques (28)(29)(30)(31)(32)(42)(43)(44)(45)(46). We also used a potentially novel, more sensitive analysis method that entails a straightforward division of T2W by T1W images to enhance waterbased contrast (39,40).…”

Fetal programming of human energy homeostasis brain networks: Issues and considerations

“…The salience network is centered on bilateral orbital frontoinsular and dorsal anterior cingulate cortices, 77 with connectivity to the VTA, thalamus, hypothalamus, and amygdala. This network is also likely important for switching between internal (default mode network) and external (central executive network) modes of thought, 78,79 a property consistent with and necessary in the context of feeding behaviors 80 . Critically, structural and functional variation in the salience network has been shown to predict food intake under stressful conditions and has been associated with familial obesity risk, and differences have been described between normal‐weight and individuals with obesity 81 .…”

Strategies to Understand the Weight‐Reduced State: Genetics and Brain Imaging

“…The role of intrinsic connectivity networks in appetite and body weight regulation is not yet fully understood. A recent study by Sewaybricker et al supported a role for the salience network in feeding and appetite regulation (91). The salience network encompasses a group of nodes (e.g., anterior insula, hypothalamus, ventral tegmental area, prefrontal cortex) that take in interceptive information from the body and then marshal our attentional and cognitive resources to address the greatest immediate homeostatic need (92).…”

“…The role of intrinsic connectivity networks in appetite and body weight regulation is not yet fully understood. A recent study by Sewaybricker et al supported a role for the salience network in feeding and appetite regulation (91).…”