Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training.

SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study.

Objective: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET).

Research Design And Methods: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

New improved radiometabolite analysis method for [F]FTHA from human plasma: a test-retest study with postprandial and fasting state.

Background: Fatty acid uptake can be measured using PET and 14-(R,S)-[F]fluoro-6-thia-heptadecanoic acid ([F]FTHA). However, the relatively rapid rate of [F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [F]FTHA (parent fraction).

Lower abdominal adipose tissue cannabinoid type 1 receptor availability in young men with overweight.

Objective: Cannabinoid type 1 receptors (CB1R) modulate feeding behavior and energy homeostasis, and the CB1R tone is dysgulated in obesity. This study aimed to investigate CB1R availability in peripheral tissue and brain in young men with overweight versus lean men.

Methods: Healthy males with high (HR, n = 16) or low (LR, n = 20) obesity risk were studied with fluoride 18-labeled FMPEP-d positron emission tomography to quantify CB1R availability in abdominal adipose tissue, brown adipose tissue, muscle, and brain.

Obesity risk is associated with brain glucose uptake and insulin resistance.

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 risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes.

Gata2, Nkx2-2 and Skor2 form a transcription factor network regulating development of a midbrain GABAergic neuron subtype with characteristics of REM-sleep regulatory neurons.

The midbrain reticular formation (MRF) is a mosaic of diverse GABAergic and glutamatergic neurons that have been associated with a variety of functions, including sleep regulation. However, the molecular characteristics and development of MRF neurons are poorly understood. As the transcription factor, Gata2 is required for the development of all GABAergic neurons derived from the embryonic mouse midbrain, we hypothesized that the genes expressed downstream of Gata2 could contribute to the diversification of GABAergic neuron subtypes in this brain region.

Cool-Water Immersion Reduces Postexercise Quadriceps Femoris Muscle Perfusion More Than Cold-Water Immersion.

Purpose: The muscle perfusion response to postexercise cold-water immersion (CWI) is not well understood. We examined the effects of graded postexercise CWI upon global and regional quadriceps femoris muscle perfusion using positron emission tomography and [15O]H2O.

Methods: Using a matched-group design, 30 healthy men performed cycle ergometer exercise at 70% V̇O2peak to a core body temperature of 38°C, followed by either 10 min of CWI at 8°C, 22°C, or seated rest (control).

Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.

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.

Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB receptor availability.

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.

Secretin activates brown fat and induces satiation.

Brown adipose tissue (BAT) thermogenesis is activated by feeding. Recently, we revealed a secretin-mediated gut-BAT-brain axis, which stimulates satiation in mice, but the purpose of meal-induced BAT activation in humans has been unclear. In this placebo-controlled, randomized crossover study, we investigated the effects of intravenous secretin on BAT metabolism (measured with [F]FDG and [O]HO positron emission tomography) and appetite (measured with functional magnetic resonance imaging) in healthy, normal weight men (GUTBAT trial no.

Assessment of a digital and an analog PET/CT system for accurate myocardial perfusion imaging with a flow phantom.

Unlabelled: In Myocardial Perfusion Imaging (MPI) with Positron Emission Tomography/Computed Tomography (PET/CT) systems, accurate quantification is essential. We assessed flow quantification accuracy over various injected activities using a flow phantom.

Methods: The study was performed on the digital 4-ring Discovery MI (DMI-20) and analog Discovery 690 (D690) PET/CT systems, using 325-1257 MBq of [O]HO.

Molecular Fingerprint and Developmental Regulation of the Tegmental GABAergic and Glutamatergic Neurons Derived from the Anterior Hindbrain.

Tegmental nuclei in the ventral midbrain and anterior hindbrain control motivated behavior, mood, memory, and movement. These nuclei contain inhibitory GABAergic and excitatory glutamatergic neurons, whose molecular diversity and development remain largely unraveled. Many tegmental neurons originate in the embryonic ventral rhombomere 1 (r1), where GABAergic fate is regulated by the transcription factor (TF) Tal1.

Kainate Receptor Auxiliary Subunit NETO2-Related Cued Fear Conditioning Impairments Associate with Defects in Amygdala Development and Excitability.

NETO2 is an auxiliary subunit for kainate-type glutamate receptors that mediate normal cued fear expression and extinction. Since the amygdala is critical for these functions, we asked whether mice have compromised amygdala function. We measured the abundance of molecular markers of neuronal maturation and plasticity, parvalbumin-positive (PV), perineuronal net-positive (PNN), and double positive (PVPNN) cells in the amygdala.

Ruthenium-Mediated F-Fluorination and Preclinical Evaluation of a New CB Receptor Imaging Agent [F]FPATPP.

Cannabinoid receptor 1 (CB1R) controls various physiological and pathological conditions, including memory, motivation, and inflammation, and is thus an interesting target for positron emission tomography (PET). Herein, we report a ruthenium-mediated radiolabeling synthesis and preclinical evaluation of a new CB1R specific radiotracer, [F]FPATPP. [F]FPATPP was produced with 16.

Automated GMP production and long-term experience in radiosynthesis of CB tracer [ F]FMPEP-d.

Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB receptor imaging tracer (3R,5R)-5-(3-([ F]fluoromethoxy-d )phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([ F]FMPEP-d ), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic F-fluorination of an alkylating agent and its GC purification, the subsequent F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the F-fluoroalkylated product, and its formulation for injection.

Changes in quadriceps femoris muscle perfusion following different degrees of cold-water immersion.

We examined the influence of graded cold-water immersion (CWI) on global and regional quadriceps muscle perfusion with positron emission tomography (PET) and [O]HO. In 30 healthy men [33 ± 8 yr; 81 ± 10 kg; 184 ± 5 cm; percentage body fat: 13 ± 5%; peak oxygen uptake (V̇o): 47 ± 8 mL·kg·min] quadriceps perfusion, thigh and calf cutaneous vascular conductance (CVC), intestinal, muscle, and local skin temperatures, thermal comfort, mean arterial pressure, and heart rate were assessed before and after 10 min of CWI at 8°C, 15°C, or 22°C. Global quadriceps perfusion did not change beyond a clinically relevant threshold (0.

Fast and efficient copper-mediated F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying.

Background: Copper-mediated radiofluorination is a straightforward method to produce a variety of [F]fluoroarenes and [F]fluoroheteroarenes. To minimize the number of steps in the production of F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.

The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.

Objective: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.

Research Design And Methods: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA 6.

Radiosynthesis of the norepinephrine transporter tracer [ F]NS12137 via copper-mediated F-labelling.

[ F]NS12137 (exo-3-[(6-[ F]fluoro-2-pyridyl)oxy]8-azabicyclo[3.2.1]octane) is a highly selective norepinephrine transporter (NET) tracer.

Radiosynthesis and Preclinical Evaluation of an α-Adrenoceptor Tracer Candidate, 6-[F]Fluoro-marsanidine.

Purpose: The α-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α and α are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α-adrenoceptors has been limited to the α subtype.

characterization of a novel norepinephrine transporter PET tracer [F]NS12137 in adult and immature Sprague-Dawley rats.

Norepinephrine modulates cognitive processes such as working and episodic memory. Pathological changes in norepinephrine and norepinephrine transporter (NET) function and degeneration of the locus coeruleus produce irreversible impairments within the whole norepinephrine system, disrupting cognitive processes. Monitoring these changes could enhance diagnostic accuracy and support development of novel therapeutic components for several neurodegenerative diseases.

[F]F-DPA for the detection of activated microglia in a mouse model of Alzheimer's disease.

Introduction: Neuroinflammation is associated with several neurological disorders, including Alzheimer's disease (AD). The translocator protein 18 kDa (TSPO), due to its overexpression during microglial activation and relatively low levels in the brain under normal neurophysiological conditions, is commonly used as an in vivo biomarker for neuroinflammation. Reported here is the preclinical evaluation of [F]F-DPA, a promising new TSPO-specific radioligand, as a tool for the detection of activated microglia at different ages in the APP/PS1-21 mouse model of AD and a blocking study to determine the specificity of the tracer.

[F]FMPEP-d PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease.

Contradictory findings on the role of the type 1 cannabinoid receptor (CBR) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CBR brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CBR, [F]FMPEP-d. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CBR immunohistochemistry with additional mice.