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.

Eating behavior varies greatly between individuals, but the neurobiological basis of these trait-like differences in feeding remains poorly understood. Central μ-opioid receptors (MOR) and cannabinoid CB1 receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain’s opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating—individuals with low MORs reported being more likely to eat in response to environment’s palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically in brain regions regulating food reward, they have distinct roles in mediating individual feeding patterns. Central MOR system might provide a pharmacological target for reducing individual’s excessive cue-reactive eating behavior.

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. We measured healthy male subjects’ (n = 52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n = 108) of anatomical MR images provided limited evidence for positive association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

Renal sinus fat is a fat depot at the renal hilum. Because of its location around the renal artery, vein, and lymphatic vessels, an expanded renal sinus fat mass may have hemodynamic and renal implications. We studied whether renal sinus fat area (RSF) associates with hypertension and whether following bariatric surgery a decrease in RSF associates with improvement of hypertension. A total of 74 severely obese and 46 lean controls were studied with whole-body magnetic resonance imaging (MRI). A total of 42 obese subjects were re-studied six months after bariatric surgery. RSF was assessed by two independent researchers using sliceOmatic. Glomerular filtration rate (eGFR) was estimated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Patients with obesity accumulated more RSF compared to lean controls (2.3 [1.7–3.1] vs. 1.8 [1.4–2.5] cm2, p = 0.03). Patients with hypertension (N = 36) had a larger RSF depot compared to normotensive subjects (2.6 [2.0–3.3] vs. 2.0 [1.4–2.5] cm2, p = 0.0007) also after accounting for body mass index (BMI). In the pooled data, RSF was negatively associated with eGFR (r = −0.20, p = 0.03), whereas there was no association with systolic or diastolic blood pressure. Following bariatric surgery, RSF was reduced (1.6 [1.3–2.3] vs. 2.3 [1.7–3.1] cm2, p = 0.03) along with other markers of adiposity. A total of 9/27 of patients achieved remission from hypertension. The remission was associated with a larger decrease in RSF, compared to patients who remained hypertensive (−0.68 [−0.74 to −0.44] vs. −0.28 [−0.59 to 0] cm2, p = 0.009). The accumulation of RSF seems to be involved in the pathogenesis of hypertension in obesity. Following bariatric surgery, loss of RSF was associated with remission from hypertension.

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. However, there is no in vivo evidence for the contribution of MOR system on human sex drive. Here we measured healthy male subjects’ (n=52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that MOR system modulates individual differences in sex drive in human males.

Objective: To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis, and whole-body insulin sensitivity occur in young adults in pre-obese state. Methods: Healthy males with either high (HR, n = 19) or low risk (LR, n = 22) for developing obesity were studied with [18F]fluoro-D-glucose ([18F]FDG) - positron emission tomography (PET) during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes. Brain, skeletal muscle, brown adipose tissue (BAT), visceral (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) glucose uptake (GU) rates were measured. Endogenous glucose production (EGP) was calculated by subtracting the exogenous glucose infusion rate from the rate of disappearance of [18F]FDG. BGU were analyzed using statistical parametric mapping (SPM), and peripheral tissue activity was determined using Carimas Software imaging processing platform. Results: BGU was higher in the HR versus LR group, and correlated inversely with whole-body insulin sensitivity (M value) in the HR but not in the LR group. Insulin-suppressed EGP did not differ between the groups, but correlated positively with BGU in the whole population and the correlation was driven by the HR group. Skeletal muscle, BAT, VAT, abdominal and femoral SAT GU were lower in the HR as compared to the LR group. Muscle GU correlated negatively with BGU in the HR but not in the LR group. Conclusion: Increased BGU, alterations in insulin action in the brain-liver axis and decreased whole-body insulin sensitivity occur early in pre-obese state.

IntroductionCentral μ-opioid receptors (MORs) modulate affective responses to physical exercise. Individuals with higher aerobic fitness report greater exercise-induced mood improvements than those with lower fitness, but the link between cardiorespiratory fitness and the MOR system remains unresolved. Here we tested whether maximal oxygen uptake (V̇O2peak) and physical activity level are associated with cerebral MOR availability and whether these phenotypes predict endogenous opioid release after a session of exercise.MethodsWe studied 64 healthy lean men who performed a maximal incremental cycling test for V̇O2peak determination, completed a questionnaire assessing moderate-to-vigorous physical activity (MVPA; in minutes per week), and underwent positron emission tomography with [11C]carfentanil, a specific radioligand for MOR. A subset of 24 subjects underwent additional positron emission tomography scan also after a 1-h session of moderate-intensity exercise and 12 of them also after a bout of high-intensity interval training.ResultsHigher self-reported MVPA level predicted greater opioid release after high-intensity interval training, and both V̇O2peak and MVPA level were associated with a larger decrease in cerebral MOR binding after aerobic exercise in the ventral striatum, orbitofrontal cortex, and insula. That is, more trained individuals showed greater opioid release acutely after exercise in brain regions especially relevant for reward and cognitive processing. Fitness was not associated with MOR availability.ConclusionsWe conclude that regular exercise training and higher aerobic fitness may induce neuroadaptation within the MOR system, which might contribute to improved emotional and behavioral responses associated with long-term exercise.