Explore the vast range of titles available.

A new study investigates brown adipose tissue (BAT) volume in young, metabolically healthy adults. The focus is on the associations between BAT volume and BMI, waist circumference, whole-body adipose tissue mass, visceral adipose tissue mass and cold-induced BAT activity. Of note, the reported associations differed in men and women.

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

The endogenous μ-opioid receptor (MOR) system regulates motivational and hedonic processing. We tested directly whether individual differences in MOR are associated with neural reward responses to food pictures in humans. We scanned 33 non-obese individuals with positron emission tomography (PET) using the MOR-specific radioligand [ 11 C]carfentanil. During a functional magnetic resonance imaging (fMRI) scan, the subjects viewed pictures of appetizing versus bland foods to elicit reward responses. MOR availability was measured in key components of the reward and emotion circuits and used to predict BOLD-fMRI responses to foods. Viewing palatable versus bland foods activates regions involved in homeostatic and reward processing, such as amygdala, ventral striatum, and hypothalamus. MOR availability in the reward and emotion circuit is negatively associated with the fMRI reward responses. Variation in MOR availability may explain why some people feel an urge to eat when encountering food cues, increasing risk for weight gain and obesity. μ-opioid signalling has a known role in the response to various rewarding stimuli, including pleasant foods. Here, Nummenmaa et al. show using PET and fMRI that individual differences in brain μ-opioid receptor density predict the strength of the neural response to highly palatable foods in humans

Alterations in the brain’s μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. We compiled [11C]carfentanil positron emission tomography scans from 204 individuals with no neurologic or psychiatric disorders, and estimated the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential using between-subject regression analysis. We also examined hemispheric differences in MOR availability. Older age was associated with increase in MOR availability in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders. Lateralized MOR system may reflect hemispheric work specialization in central emotion and pain processes. •Sex, age and smoking have regionally specific influence on human μ-opioid receptor (MOR) availability in the brain.•MOR availabilities have regional asymmetries between the two hemispheres, right hemisphere being more abundant in MORs.•Variability in MOR system may explain why some individuals are vulnerable to chronic pain and neuropsychiatric disorders.

Brown adipose tissue helps maintain normal body temperature in newborn humans but was thought to be absent in healthy adults. This report shows the presence of substantial amounts of metabolically active brown adipose tissue, as documented by biochemical, molecular, and morphologic criteria, and by a cold-induced glucose uptake in paracervical and supraclavicular adipose tissue that was increased by a factor of 15. This report shows the presence of substantial amounts of metabolically active brown adipose tissue, as documented by biochemical, molecular, and morphologic criteria, and by a cold-induced glucose uptake in paracervical and supraclavicular adipose tissue that was increased by a factor of 15. Active brown adipose tissue helps maintain normal body temperature in newborn infants. It is believed that this tissue regresses with increasing age and is completely lost by the time a person reaches adulthood. 1 However, the capacity to produce brown adipose tissue in adulthood has been shown in patients with catecholamine-secreting tumors such as pheochromocytomas and paragangliomas, in whom distinct brown-adipose-tissue depots develop. 2 , 3 When scanning with a combination of PET and computed tomography (CT) — with the glucose analogue 18 F-fluorodeoxyglucose ( 18 F-FDG) as a tracer — is used in the diagnosis of neoplasms and their metastases, the results can be . . .

Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain’s MOR availability was measured with positron emission tomography (PET) using an agonist radioligand [11C]carfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.

Activation of thermogenic brown and beige adipocytes is considered as a strategy to improve metabolic control. Here, we identify GPR180 as a receptor regulating brown and beige adipocyte function and whole-body glucose homeostasis, whose expression in humans is associated with improved metabolic control. We demonstrate that GPR180 is not a GPCR but a component of the TGFβ signalling pathway and regulates the activity of the TGFβ receptor complex through SMAD3 phosphorylation. In addition, using genetic and pharmacological tools, we provide evidence that GPR180 is required to manifest Collagen triple helix repeat containing 1 (CTHRC1) action to regulate brown and beige adipocyte activity and glucose homeostasis. In this work, we show that CTHRC1/GPR180 signalling integrates into the TGFβ signalling as an alternative axis to fine-tune and achieve low-grade activation of the pathway to prevent pathophysiological response while contributing to control of glucose and energy metabolism. Activation of thermogenic adipocytes is a strategy to combat metabolic diseases. Here the authors report that GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1, and contributes to the regulation of glucose and energy metabolism.

Purpose Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [ 15 O]O 2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE. Methods Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [ 15 O]O 2 , [ 15 O]H 2 O, and [ 18 F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold. Results BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2–47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus. Conclusion Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.

•We developed a large-scale atlas of human type 2 dopamine receptor (D2R).•D2R availability decreases similarly among males and females and overall females have a higher availability than males through age.•Potential sex-dependencies in D2R expression may predispose males and females to different neuropsychiatric conditions.•Striatal [11C]raclopride binding potential can be calculated reliably from positron emission tomography (PET) scan without magnetic resonance image (MRI). The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

Background and Aim:The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron emission tomography (PET). The aim of this study was to use proton magnetic resonance spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of BAT and white adipose tissue (WAT) are associated with BAT metabolic activity determined by deoxy-2-18F-fluoro-d-glucose (18F-FDG)-PET.Materials and Methods:Ten healthy subjects (four women, six men; 25 to 45 years of age) were studied using PET–magnetic resonance imaging during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on eight subjects.Results:The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid-burning capacity of BAT associated with whole-body insulin sensitivity. During cold exposure, the FF of BAT was lower than at room temperature, and cold-induced FF of BAT associated inversely with high-density lipoprotein and directly with low-density lipoprotein cholesterol.Conclusion:Both 1H MRS–derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid-burning capacity of BAT and whole-body insulin sensitivity emphasizes the role of BAT in glucose handling. Furthermore, the relation of FF to high-density lipoprotein and low-density lipoprotein cholesterol suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.BAT and WAT was studied with 1H-MRS and 18-F-FDG PET. Temperature and FF from 1H-MRS correlated with PET. 1H-MRS thermometry and FF are promising tools to study BAT activity.