Obesity-mediated inflammation may damage the brain circuit that regulates food intake

Abstract

Adiposity is associated with chronic low-grade systemic inflammation and increased inflammation in the hypothalamus, a key structure in feeding behavior. It remains unknown whether inflammation impacts other brain structures that regulate feeding behavior. We studied 44 overweight/obese and 19 lean individuals with MRI and plasma fibrinogen levels (marker of inflammation). We performed MRI-based segmentations of the medial and lateral orbitofrotal cortex (OFC) and hippocampal volumes. Gray matter (GM) volumes were adjusted for head size variability. We conducted logistic and hierarchical regressions to assess the association between fibrinogen levels and brain volumetric data. Using diffusion tensor imaging (DTI), we created apparent diffusion coefficient (ADC) maps and conducted voxelwise correlational analyses. Fibrinogen concentrations were higher among the overweight/obese (t[61]=-2.33, P=0.023). Lateral OFC associated together with fibrinogen correctly classified those with excess of weight (accuracy=76.2%, sensitivity=95.5%, specificity=31.6%). The lateral OFC volumes of overweight/obese were negatively associated with fibrinogen (r=-0.37, P=0.016) and after accounting for age, hypertension, waist/hip ratio and lipid and sugar levels, fibrinogen significantly explained an additional 9% of the variance in the lateral OFC volume (β=-0.348, ΔR2=0.093, ΔF P=0.046). Among overweight/obese the associations between GM ADC and fibrinogen were significantly positive (P<0.001) in the left and right amygdala and the right parietal region. Among lean individuals these associations were negative and located in the left prefrontal, the right parietal and the left occipital lobes. This is the first study to report that adiposity-related inflammation may reduce the integrity of some of the brain structures involved in reward and feeding behaviors.

The Role of Diffusion Tensor Imaging in the Study of Cognitive Aging

“…A second study noted that individuals with longstanding type 1 diabetes had significantly reduced FA relative to matched controls; moreover, in the diabetic individuals, longer disease duration and poorer glucose regulation was correlated with reduced FA (Kodl et al 2008). A third study linked adiposity to reduced white matter integrity on DTI (Cazettes et al 2011); this and another study found associations between decreased white matter integrity and increases in markers of systemic inflammation that commonly accompanies cerebrovascular dysfunction (Wersching et al 2010). While these studies may have implications for the hypothesis that at least part of the age-associated declines in white matter integrity may be driven by the effects of hypertension, type two diabetes, obesity, and other cardiovascular risk factors even in the absence of an acute cerebrovascular event, a great deal more study is required to further substantiate this view.…”

Cognitive and autonomic determinants of energy homeostasis in obesity

“…35 The importance of forebrain integrity in obesity develop ment is substantiated by the association between obesity and the loss of grey matter in these cortical regions. [36][37][38] Whether the loss of grey matter follows or predates obesity is still under investigation. Obesity, at least in its visceral form, might induce cortical thinning, 36 which could be secondary to inflammatory processes.…”

Obesity, a burning problem

“…Obesity is related to type II diabetes, hypertension, dyslipaedaemia and cardiovascular diseases (CVD) 1,2,3,7,8 . The endocannabinoid system (ECS) is involved in lipid metabolism and obesity.…”

“…Adiposity is associated with chronic low-grade systemic inflammation as well as increased inflammation of the hypothalamus. Inflammation of hypothalamus may reduce the integrity of structures involved in reward and feeding behaviours 8 and this may alter the feeding behaviors.…”