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.

Background Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. Methods Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects’ physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. Results Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). Conclusions These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.