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Brain free fatty acid uptake is elevated in morbid obesity, and is irreversible 6 months after bariatric surgery: A positron emission tomography study
<h3>Aim</h3><p>To 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.</p><h3>Materials and ...
A Partial Loss-of-Function Variant in AKT2 is Associated with Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin Sensitive Tissues: a Genotype-Based Callback Positron Emission Tomography Study
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</p><p>Rare fully penetrant mutations in AKT2 are an established cause of monogenic disorders of glucose metabolism. Recently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was identified that ...
Interindividual variability and lateralization of mu-opioid receptors in the human brain
Alterations in the brain's mu-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological ...
Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight
Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between ...
Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability
<h3>Background</h3><p>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 CB<sub>1</sub> receptors (CB<sub>1</sub>Rs) are associated with risk for developing obesity.</p><h3>Methods</h3><p>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 [<sup>18</sup>F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [<sup>11</sup>C]carfentanil and CB<sub>1</sub>Rs with [<sup>18</sup>F]FMPEP-d<sub>2</sub>.</p><h3>Results</h3><p>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 CB<sub>1</sub>Rs (36 subjects).</p><h3>Conclusions</h3><p>These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.</p>...
μ-opioid receptor availability is associated with sex drive in human males
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 ...
Obesity risk is associated with brain glucose uptake and insulin resistance
<p><strong>Objective: </strong>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.</p><p>< ...
Cerebral μ-opioid and CB1 receptor systems have distinct roles in human feeding behavior
<p>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 CB<sub>1</sub> receptors (CB<sub>1</sub>R) 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 CB<sub>1</sub>R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [<sup>11</sup>C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [<sup>18</sup>F]FMPEP-d<sub>2</sub> scans of CB<sub>1</sub>Rs from 35 subjects (all males, all also included in the [<sup>11</sup>C]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. CB<sub>1</sub>R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB<sub>1</sub>Rs 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.<br></p>...
Novel Effects of the Gastrointestinal Hormone Secretin on Cardiac Metabolism and Renal Function
<p>The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [<sup>18</sup>F]2-fluoro-2-deoxy-D-glucose ([<sup>18</sup>F]FDG) positron emission tomography. Kidney function was measured with [<sup>18</sup>F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared to placebo (secretin vs. placebo, mean + standard deviation, 15.5 ± 7.4 vs. 9.7 ± 4.9 μmol/100g/min, 95% confidence interval (CI) [2.2, 9.4], p=0.004). Secretin also increased [<sup>18</sup>F]FDG renal clearance (44.5 ± 5.4 vs. 39.5 ± 8.5 ml/min, 95%CI[1.9, 8.1], p=0.004) and eGFR was significantly increased from baseline after secretin, compared to placebo (17.8 ± 9.8 vs. 6.0 ± 5.2 Δml/min/1.73m<sup>2</sup>, 95%CI[6.0, 17.6], p=0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.</p>...