Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects

Abstract

Context: Growing evidence implicates hypothalamic inflammation in the pathogenesis of dietinduced obesity and cognitive dysfunction in rodent models. Few studies have addressed the association between obesity and hypothalamic damage in humans and its relevance. Objective: This study aimed to determine markers of obesity-associated hypothalamic damage on diffusion tensor imaging (DTI) and to determine whether DTI metrics are associated with performance on cognitive testing. Design and Participants: This cross-sectional study analyzed DTI metrics (primary [γ1], secondary [γ2], and tertiary [γ3] eigenvalues; fractional anisotropy; and mean diffusivity) in the hypothalamus of 24 consecutive middle-age obese subjects (13 women; 49.8 ± 8.1 y; body mass index [BMI], 43.9 ± 0.92 kg/m2) and 20 healthy volunteers (10 women; 48.8 ± 9.5 y; BMI, 24.3 ± 0.79 kg/m2). Outcome: measures: Hypothalamic damage assessed by DTI metrics and cognitive performance evaluated by neuropsychological test battery. Results: γ1 values in the hypothalamus were significantly lower in obese subjects (P < .0001). The sensitivity, specificity, and positive and negative predictive values for obesity-associated hypothalamic damage by γ1 < 1.072 were 75, 87.5, 83.3, and 80.7%, respectively. Patients with hypothalamic γ1 < 1.072 had higher values of BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests. Combined BMI and alanine aminotransferase had the strongest association with hypothalamic damage reflected by γ1 < 1.072 (area under the curve = 0.89). Conclusions: DTI detectsobesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance. This study highlights the potential utility of γ1 as a surrogate marker of obesity-associated hypothalamic damage.