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J Clin Endocrinol Metab. 2015 Feb;100(2):E276-81. doi: 10.1210/jc.2014-2682. Epub 2014 Nov 25.

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

Author information

1
Department of Radiology (J.P., G.B., X.M., S.P.), Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta. Girona, Spain; Department of Computer Science, Applied Mathematics and Statistics (J.D.-i.-E.), University of Girona. Girona, Spain; Department of Diabetes, Endocrinology and Nutrition (J.P., G.X., W.R., J.M.F.-R.), IDIBGI, Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn). Girona, Spain; and Department of Psychiatry (F.F.-A.), Hospital Universitari de Bellvitge, and CIBERobn, Barcelona, Spain.

Abstract

CONTEXT:

Growing evidence implicates hypothalamic inflammation in the pathogenesis of diet-induced 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 [λ(1)], secondary [λ(2)], and tertiary [λ(3)] 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/m(2)) and 20 healthy volunteers (10 women; 48.8 ± 9.5 y; BMI, 24.3 ± 0.79 kg/m(2)).

OUTCOME:

measures: Hypothalamic damage assessed by DTI metrics and cognitive performance evaluated by neuropsychological test battery.

RESULTS:

λ(1) 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 λ(1) < 1.072 were 75, 87.5, 83.3, and 80.7%, respectively. Patients with hypothalamic λ(1) < 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 λ(1) < 1.072 (area under the curve = 0.89).

CONCLUSIONS:

DTI detects obesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance. This study highlights the potential utility of λ(1) as a surrogate marker of obesity-associated hypothalamic damage.

PMID:
25423565
DOI:
10.1210/jc.2014-2682
[Indexed for MEDLINE]

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