Brain free fatty acid uptake is elevated in morbid obesity, and is irreversible 6 months after bariatric surgery: A positron emission tomography study

Abstract

AimTo investigate whether there are differences in brain fatty acid uptake (BFAU) between morbidly obese and lean subjects, and the effect of weight loss following bariatric surgery.Materials and methodsWe measured BFAU with 14(R, S)‐[18F]fluoro‐6‐thia‐heptadecanoic acid and positron emission tomography in 24 morbidly obese and 14 lean women. Obese subjects were restudied 6 months after bariatric surgery. We also assessed whether there was hypothalamic neuroinflammation in the obese subjects using fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging.ResultsObese subjects had a higher BFAU than lean subjects (1.12 [0.61] vs. 0.72 [0.50] μmol 100 g−1 min−1, P = 0.0002), driven by higher fatty acid uptake availability. BFAU correlated positively with BMI (P = 0.006, r = 0.48), whole body fatty acid oxidation (P = 0.006, r = 0.47) and leptin levels (P = 0.001, r = 0.54). When BFAU, leptin and body mass index (BMI) were included in the same model, the association between BFAU and leptin was the strongest. BFAU did not correlate with FLAIR‐derived estimates of hypothalamic inflammation. Six months after bariatric surgery, obese subjects achieved significant weight loss (−10 units of BMI). BFAU was not significantly changed (1.12 [0.61] vs. 1.09 [0.39] μmol 100 g−1 min−1, ns), probably because of the ongoing catabolic state. Finally, baseline BFAU predicted worse plasma glucose levels at 2 years of follow‐up.ConclusionsBFAU is increased in morbidly obese compared with lean subjects, and is unchanged 6 months after bariatric surgery. Baseline BFAU predicts worse plasma glucose levels at follow‐up, supporting the notion that the brain participates in the control of whole‐body homeostasis.

Brain insulin sensitivity is linked to body fat distribution—the positron emission tomography perspective

“…We have previously reported in two different datasets with subjects undergoing bariatric surgery that increased brain substrate uptake (glucose or free fatty acids) before surgery predicts a worse glycemic control at follow-up [6,9]. This finding is in line with the longitudinal findings of Kullmann and colleagues: brain insulin resistance and/or higher brain substrate uptake at baseline predicts an unfavorable metabolic outcome at follow-up.…”

Using quantitative imaging to determine the correlation between hypothalamic inflammation and anxiety and depression in young patients with obesity

“…We also analyzed the T2-MRI data to assess whether BMI and SAS and SDS scores were associated with the H/A SI ratio. Regarding the correlations with BMI in this study, we were not able to replicate the results of previous studies (21)(22)(23); this may be due to our small sample size or other technical reasons (24). The hypothalamus is a very small brain region, and our T2-MRI sequence was protocoled to cover the whole brain with 3 mm thick slices.…”

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

“…This finding is in line with the established notion that worse metabolic control is associated with more severe insulin resistance. FFAs cross the blood-brain barrier, and we have previously shown that obese patients have increased brain FFA uptake as compared with lean individuals ( 36 ). On the basis of previous studies showing that hypothalamic sensing of circulating FFAs is important in the control of nutrient intake and energy balance ( 37 ), we hypothesized that FFAs could be key players in the cross-talk between brain and peripheral tissues in the context of insulin resistance.…”