whole-body-regional-quantification-active-human-brown-adipose-tissue

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using <sup>18</sup>F-FDG PET/CT

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT&#39;s ability to ...

an-implantable-system-for-chronic-in-vivo-electromyography

An Implantable System For Chronic In Vivo Electromyography

Electromyography (EMG) measures the muscle response to electrical stimulation or spontaneous activity of motor units and plays an important role in ...

National Institutes of Health

Vanderbilt University Medical Center

This study evaluates how extraesophageal reflux affects membranous vocal fold healing in a canine model. We created membranous vocal fold injuries in the animals and randomly assigned them to topical application of acid and pepsin at pH 2 or pH 6 or of normal saline solution every other day for 12 days. The experimental vocal folds were compared to uninjured, control vocal folds from animals painlessly sacrificed for other reasons. Hematoxylin and eosin, fibronectin, and procollagen I staining were performed for histologic analysis. The injured specimens had three times greater cellular infiltrate (p < or = .001, analysis of variance) and twice as much fibronectin and procollagen I (p < or = .001, analysis of variance) as did the specimens from the control animals. No significant differences or trends were identified for cellular infiltrate, fibronectin, or procollagen I within the injured groups (p > .05, Bonferroni t-test). Acute wound healing did not appear to be influenced by the presence of acid and pepsin at pH 2 or 6 as compared to saline solution.

Acute histologic effects of extraesophageal reflux on vocal fold healing.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy.

Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS.

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m; 8 obese, BMI 34.8 ± 3.3 kg/m] after 5 h of tolerable cold exposure, we measured BAT volume and activity by F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

Mapping of human brown adipose tissue in lean and obese young men.

β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUV] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.

Shan Huang

National Cancer Institute

National Institutes of Health

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using ¹⁸F-FDG PET/CT

An Implantable System For Chronic In Vivo Electromyography

Shan Huang

National Cancer Institute

National Institutes of Health

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

An Implantable System For Chronic In Vivo Electromyography

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using ¹⁸F-FDG PET/CT