Dyslipidemia links obesity to early cerebral neurochemical alterations


  • Disclosures: Dr. Haley is funded by the American Heart Association, the American Federation for Aging Research, and the National Institute of Neurological Disorders and Stroke. Ms. Gonzales is funded by the National Institute on Aging. Mr. Tarumi reports no disclosures. Dr. Tanaka has received research support from the American Heart Association.

  • Funding agencies: This study was funded in part by the American Heart Association (09BGIA2060722, APH), the American Federation for Aging Research (8A0024, APH), the National Institute of Neurological Disorders and Stroke (R01NS75565, APH), and the National Institute on Aging (F31AG040890, MMG.).



To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry.

Design and Methods

Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry.


Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation.


Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity.