Brain structure predicts risk for obesity

Abstract

The neurobiology of obesity is poorly understood. Here we report findings of a study designed to examine the differences in brain regional gray matter volume in adults recruited as either Obese Prone or Obese Resistant based on self-identification, body mass index, and personal/family weight history. Magnetic resonance imaging was performed in 28 Obese Prone (14 male, 14 female) and 25 Obese Resistant (13 male, 12 female) healthy adults. Voxel-based morphometry was used to identify gray matter volume differences between groups. Gray matter volume was found to be lower in the insula, medial orbitofrontal cortex and cerebellum in Obese Prone, as compared to Obese Resistant individuals. Adjusting for body fat mass did not impact these results. Insula gray matter volume was negatively correlated with leptin concentration and measures of hunger. These findings suggest that individuals at risk for weight gain have structural differences in brain regions known to be important in energy intake regulation, and that these differences, particularly in the insula, may be related to leptin.

Introduction

Obesity is a serious public health problem of dramatically rising prevalence in recent decades in the United States and the world, with currently over 65% of adults in the U.S. classified as either overweight or obese (Flegal et al., 2012, Shields et al., 2011). Early studies of obesity focused on metabolic differences between obese and non-obese persons; however, advances in structural and functional neuroimaging techniques have recently begun to shed light on neuroanatomical and neurophysiological factors that may be related to obesity.

Most functional magnetic resonance imaging (fMRI) studies on obesity have focused on how the condition alters the cortical response to food cues (Carnell et al., 2012, Cornier, 2011, Cornier et al., 2009, Martin et al., 2010, McCaffery et al., 2009, Neary and Batterham, 2010, Rosenbaum et al., 2008, Rothemund et al., 2007, Stoeckel et al., 2008, Van den Eynde and Treasure, 2009, Wallner-Leibmann et al., 2010). These studies have generally found increased responses to both visual and olfactory cues associated with high-calorie foods in obesity. Regions of increased response include the limbic areas such as the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula (Martin et al., 2010, Rothemund et al., 2007, Stoeckel et al., 2008). Furthermore, in a study of reduced-obese persons, i.e. formerly obese subjects who have lost weight, a decreased ability to “turn off” response to food cues after overfeeding was observed compared to thin controls (Cornier et al., 2009). These studies suggest that obesity is not only associated with altered response to food cues, but also a deficit in the ability to modulate this response based on metabolic need.

In a small number of studies, MRI has also been used to examine brain structure in human obesity. Pannacciulli et al. (2006) found that obese subjects had reduced gray matter (GM) volume in cerebellum, frontal operculum, postcentral gyrus, putamen, and middle frontal gyrus. In the same subjects, leptin concentration was also found to be negatively correlated with GM volume in the inferior frontal operculum, postcentral gyrus, and putamen, and positively correlated with GM volume in the inferior temporal gyrus and cerebellum (Pannacciulli, Le, Chen, Reiman, & Krakoff, 2007). More recent studies have shown negative correlations between GM volume and waist circumference in a variety of anterior and posterior cortical areas (Kurth et al., 2012), a negative correlation of BMI and future BMI with overall brain volume (Yokum, Ng, & Stice, 2012) and an association between reduced orbitofrontal cortex volume and executive dysfunction in obese adolescents (Maayan, Hoogendoorn, Sweat, & Convit, 2011).

Although previous neuroimaging research has shown that the obese phenotype is associated with structural and functional brain alterations, it is unknown if these changes are a core feature of the condition that gives rise to an obese phenotype, i.e. are present in “at risk” individuals, or are simply a consequence of excess body fat. Current understanding of the condition suggests that both environmental and genetic factors confer risk of obesity (Hill et al., 2000, Peters et al., 2002); however, not everyone in a similar environment is obese or overweight, suggesting that resistance to the condition must be conferred through an endogenous mechanism (Bessesen, Bull, & Cornier, 2008). In the present study, we used whole brain voxel-based morphometry (VBM) to examine structural brain differences between Obese Prone (OP) and Obese Resistant (OR) individuals. Subjects were empirically classified as OR or OP based on personal and family weight history, as defined previously (Schmidt, Harmon, Sharp, Kealey, & Bessesen, 2012). Studying OP, as opposed to already obese or reduced-obese individuals, reveals structural brain differences that may precede weight gain and obesity and therefore could be a causative mechanism and/or be used as a predictor of obesity risk. In addition to the whole-brain VBM analysis, given previous findings implicating the insula in obesity (Carnell et al., 2012, Cornier et al., 2009), we hypothesized that GM volume in this region may relate to plasma leptin concentration and ratings of hunger after a meal. Specifically, we hypothesized that these factors would predict structural differences in the insula as well as other regions essential for maintenance and awareness of homeostatic balance.