Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults.

ABSTRACTIn rodents, exercise alters the plasma concentration of exerkines that regulate white adipose tissue (WAT) browning or brown adipose tissue (BAT) metabolism. This study aims to analyse the acute and chronic effect of exercise on the circulating concentrations of 16 of these exerkines in humans. Ten young sedentary adults (6 female) performed a maximum walking effort test and a resistance exercise session. The plasma concentration of 16 exerkines was assessed before, and 3, 30, 60, and 120 min after exercise. Those exerkines modified by exercise were additionally measured in another 28 subjects (22 women). We also measured the plasma concentrations of the exerkines before and after a 24-week exercise programme (endurance + resistance; 3-groups: control, moderate-intensity and vigorous-intensity) in 110 subjects (75 women). Endurance exercise acutely increased the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, and follistatin-like protein 1 (3 min after exercise), and musclin and fibroblast growth factor 21 (30 and 60 min after exercise), decreasing the plasma concentration of leptin (30 min after exercise). Adiponectin, atrial natriuretic peptide (ANP), ß-aminoisobutyric acid, meteorin-like, follistatin, pro-ANP, irisin and myostatin were not modified or not detectable. The resistance exercise session increased the plasma concentration of lactate 3 min after exercise. Chronic exercise did not alter the plasma concentration of these exerkines. In sedentary young adults, acute endurance exercise releases to the bloodstream exerkines that regulate BAT metabolism and WAT browning. In contrast, neither a low-volume resistance exercise session nor a 24-week training programme modified plasma levels of these molecules.HighlightsAcute endurance exercise increases the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, follistatin-like protein 1, musclin, and fibroblast growth factor 21, and decrease the plasma concentration of leptin.The exercise-induced change in lactate plasma concentration is positively associated with brown adipose tissue volume, glucose uptake and radiodensity.Neither acute resistance exercise nor chronic exercise significantly alter the plasma concentration of these exerkines.Trial registration: ClinicalTrials.gov identifier: NCT02365129.

Higher Physical Activity Is Related to Lower Neck Adiposity in Young Men, but to Higher Neck Adiposity in Young Women: An Exploratory Study.

The role of lifestyle behaviors on neck adipose tissue (NAT), a fat depot that appears to be involved in the pathogenesis of different cardiometabolic diseases and in inflammatory status, is unknown. In this cross-sectional and exploratory study, the authors examined the relationship between sedentary time and physical activity (PA) with neck adiposity in young adults. A total of 134 subjects (69% women, 23 ± 2 years) were enrolled. The time spent in sedentary behavior and PA of different intensity were objectively measured for 7 consecutive days (24 hr/day), using a wrist (nondominant)-worn accelerometer. The NAT volume was assessed using computed tomography, and the compartmental (subcutaneous, intermuscular, and perivertebral) and total NAT volumes were determined at the level of vertebra C5. Anthropometric indicators and body composition (by dual-energy X-ray absorptiometry) were determined. The time spent in light physical activity and moderate physical activity (MPA) and the overall PA were inversely associated with the intermuscular NAT volume in men, as were the MPA and overall PA with total NAT volume (all ps ≤ .04). Sedentary time was directly related to the total NAT volume (p = .04). An opposite trend was observed in women, finding a direct relationship of MPA with the subcutaneous NAT; of light physical activity, MPA, and overall PA with the perivertebral NAT; and of light physical activity with total NAT volumes (all ps ≤ .05). The observed associations were weak, and after adjusting for multiplicity, the results became nonsignificant (p > .05). These findings suggest that the specific characteristics of PA (time and intensity) might have sex-dependent implications in the accumulation of NAT.

Neck adipose tissue accumulation is associated with higher overall and central adiposity, a higher cardiometabolic risk, and a pro-inflammatory profile in young adults.

OBJECTIVES: Neck adipose tissue (NAT) volume increases with general adiposity, with fat accumulating in different neck tissue compartments. In patients with certain malignant/benign tumours, the accumulation of NAT, and certain NAT distributions, have been associated with cardiometabolic risk (CMR). However, it is unknown whether the same relationships exist in healthy people, and whether NAT accumulation and distribution are related to the inflammatory status. METHODS: In this cross-sectional study, 139 young healthy adults (68% women) underwent a computed tomography scan to quantify the volume of compartmental (i.e., subcutaneous, intermuscular and perivertebral) and total NAT at the height of vertebra C5. Anthropometric indicators were measured, and body composition determined using dual energy X-ray absorptiometry. Information on CMR factors (i.e., blood glycaemic and lipid markers, blood pressure and physical fitness) was also gathered, and a CMR score calculated. Several plasma cytokines and serum components of the innate immune system were measured to determine the inflammatory status. RESULTS: Compartmental and total NAT volumes were directly related to body mass index (BMI), and lean, fat, and visceral adipose tissue (VAT) masses (all, P ≤ 0.05). Larger compartmental (especially intermuscular) and total NAT volumes were directly associated with the CMR score, several CMR factors (i.e., glycaemic and lipid markers and blood pressure), and the C3, C4 and leptin concentrations. They were, however, inversely correlated with the CMR factors high density lipoprotein-cholesterol (HDL-C) and physical fitness, and with the adiponectin concentration (all P ≤ 0.05). Several of these associations remained statistically significant (P ≤ 0.05) after adjustment for BMI, body fat percentage or VAT mass. Overall, results did not change after applying false discovery rate correction. CONCLUSIONS: NAT volume and its distribution among different tissue compartments is associated with the CMR and inflammatory profile of young healthy adults. Total NAT volume appears to be as valuable as VAT mass in terms of predicting CMR and inflammatory status.

Evidence of high 18 F-fluorodeoxyglucose uptake in the subcutaneous adipose tissue of the dorsocervical area in young adults.

NEW FINDINGS: What is the central question of this study? In some studies, biopsies have been performed of the subcutaneous adipose tissue in the abdomen, and they failed to find browning markers. Is the abdomen the right place to take biopsies? What is the main finding and its importance? For first time, we observed that the glucose uptake in the dorsocervical subcutaneous adipose tissue is higher in comparison to other areas of subcutaneous adipose tissue. ABSTRACT: Neonates have subcutaneous brown adipose tissue (BAT) in the dorsocervical area, and it is thought that these depots gradually disappear with age. Here, we determined that young adults have high 18 F-flurodeoxyglucose (18 F-FDG) uptake in the subcutaneous adipose tissue (SAT) of the dorsocervical area. A total of 133 young adults (age 22 ± 2 years; body mass index 25 ± 5 kg m2 ) were included in the study. We performed a shivering threshold test for every participant. Later, we performed 2 h of personalized cold exposure, immediately before a positron emission tomography/computed tomography scan. We showed that 23 of 133 participants had 18 F-FDG uptake in the dorsocervical area that achieved the criteria to be considered BAT, mainly in women (96%, n = 22 of 23). In the whole sample, the glucose uptake in the SAT of the dorsocervical area was positively correlated with BAT volume and activity located in the supraclavicular area. We showed that the 18 F-FDG uptake of the SAT of the dorsocervical area in humans is different from that of other SAT areas. Future studies are warranted to confirm the brown signature of this tissue.

Loss of Bone Mineral Density Associated with Age in Male Rats Fed on Sunflower Oil Is Avoided by Virgin Olive Oil Intake or Coenzyme Q Supplementation.

The role of dietary fat unsaturation and the supplementation of coenzyme Q have been evaluated in relation to bone health. Male Wistar rats were maintained for 6 or 24 months on two diets varying in the fat source, namely virgin olive oil, rich in monounsaturated fatty acids, or sunflower oil, rich in n-6 polyunsaturated fatty acids. Both dietary fats were supplemented or not with coenzyme Q10 (CoQ10). Bone mineral density (BMD) was evaluated in the femur. Serum levels of osteocalcin, osteopontin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), adrenocorticotropin (ACTH) and parathyroid hormone (PTH), as well as urinary F2-isoprostanes were measured. Aged animals fed on virgin olive oil showed higher BMD than those fed on sunflower oil. In addition, CoQ10 prevented the age-related decline in BMD in animals fed on sunflower oil. Urinary F2-isoprostanes analysis showed that sunflower oil led to the highest oxidative status in old animals, which was avoided by supplementation with CoQ10. In conclusion, lifelong feeding on virgin olive oil or the supplementation of sunflower oil on CoQ10 prevented, at least in part mediated by a low oxidative stress status, the age-related decrease in BMD found in sunflower oil fed animals.

Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition.

During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.

¹8F-Fluorocholine PET/CT as a complementary tool in the follow-up of low-grade glioma: diagnostic accuracy and clinical utility.

PURPOSE: The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating (18)F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility. METHODS: This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, (201)Tl-SPECT and (18)F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis. RESULTS: Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of >6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9% for aMRI (38.8% inconclusive), 69.2 % for (201)Tl-SPECT (11.1% inconclusive), and 100% for (18)F-fluorocholine PET/CT. (201)Tl-SPECT led correctly to a change in the initial approach in 38.9% of patients but might have led to error in 27.8%. The use of (18)F-fluorocholine PET/CT alone rather than (201)Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2% of patients and endorsed the approach in the remaining 27.8%. CONCLUSION: Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. (18)F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients.

OBJECTIVES: To evaluate prospectively the usefulness of the routine determination of BRAF(T1799A) mutation on thyroid fine-needle aspiration biopsy (FNAB) to detect cytopathology false negative papillary thyroid carcinomas (PTC) and, therefore, as a tool to improve the sensitivity of the preoperative cytopathological diagnosis of PTC in thyroid nodules. BACKGROUND: FNAB is the most reliable diagnostic test to discriminate between malignant and benign thyroid nodules, but nondiagnostic results remain a clinical management dilemma. BRAF(T1799A) mutation is the most prevalent genetic alteration in thyroid cancers and is specific for PTC, characteristics that make it the most potentially helpful genetic tool to improve the diagnostic accuracy of FNAB. METHODS: An exhaustive recruitment of all patients subjected to thyroid FNAB in our institution during 4 years was performed. BRAF(T1799A) mutation was determined on thyroid FNAB specimens by PCR and restriction fragment length polymorphism, plus direct sequencing in positive samples. RESULTS: BRAF(T1799A) mutation on FNAB detected 47.2% (17/36) of PTC cases. It confirmed preoperatively 45.5% (5/11) of the PTC cases in the indeterminate category and decreased the rate of cytopathology false-negatives in 33.3% (6/18), improving the combined (BRAF(T1799A) mutation + cytopathological analysis) sensitivity of the detection of PTC on FNAB in 16.7%. CONCLUSIONS: BRAF(T1799A) mutation improves the diagnosis of PTC on FNAB, mainly because of the detection of cytopathology false-negatives, and it can be helpful in the routine analysis of thyroid nodules, especially in clinical settings with moderate sensitivity to detect PTC on FNAB.

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer.

BACKGROUND: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). METHODS: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. RESULTS: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. CONCLUSIONS: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.

Thallium-201 SPECT in brain gliomas: Quantitative assessment in differential diagnosis between tumor recurrence and radionecrosis.

OBJECTIVE: To compare various published thallium-201 uptake indexes in the differential diagnosis in recurrent brain gliomas. MATERIAL AND METHODS: Thallium-201 SPECT studies were performed in 79 patients previously treated for glial tumor with clinical or radiologic suspicion of recurrence. Regions of interest were established in the tumor area and in other sites with normal uptake. RESULTS: A high linear correlation was found among indices, with significant differences between all index pairs. Logistic regression analysis confirmed high colinearity among indexes, with index 3 (mean counts in tumor/mean counts in contralateral hemisphere) showing a slightly superior predictive power to differentiate tumor absence from tumor presence and tumor absence from low-grade recurrence. These findings were supported by analysis of areas under the ROC curve. CONCLUSIONS: The uptake indices studied behave similarly in the evaluation of a possible recurrence of a glial brain lesion and should be considered complementary to visual evaluation as a semi-objective tool.

18F-fluorodeoxiglucose positron emission tomography for the evaluation of neoadjuvant therapy response in esophageal cancer: systematic review of the literature.

UNLABELLED: Neoadjuvant treatment is a relatively new therapeutic approach for locally advanced esophageal cancer. Response assessment is crucial for the treatment of these patients. Cross sectional imaging has traditionally being used as the elective method of response assessment. Recently, 18F fluorodeoxyglucose- positron emission tomography (FDG-PET) has emerged as a new valuable tool defining therapy response assessment in other tumors. AIM: We systematically reviewed the increasing number of publications appearing in the literature analyzing the utility of FDG-PET in the evaluation of neoadjuvant therapy response assessment. METHODS: We performed a bibliographic search according to the COSI protocol and selected only prospective studies to achieve the highest levels of evidence. Quality assessment was defined with the QUADAS questionnaire. RESULTS: Eight of 237 potentially relevant publications were selected for the analysis. Ranged sensitivity, specificity, positive predictive value, and negative predictive value for primary tumor response assessment were 27.3% to 93.3%, 41.7% to 95.2%, 70.8% to 93.3% and 71.4% to 93.5%, respectively, and for N restaging, 16.0% to 67.5%, 85.7% to 100%, 33% to 100% and 91.7% to 93.3%, respectively. The heterogeneity of the publications ruled out the possibility of meta-analysis. FDG-PET is more precise compared with computed tomography in the evaluation of induction therapy response assessment. CONCLUSION: FDG-PET seems to be the best available imaging modality for neoadjuvant therapy response assessment in esophageal cancer. But more prospective studies with larger populations are needed to confirm the power of this imaging tool in this aim and to determine the best analytical interpretation method and threshold to differentiate responders from nonresponding patients.

Two-phase scintigraphy with technetium 99m-sestamibi in patients with hyperparathyroidism due to chronic renal failure.

BACKGROUND: The objective of the current study was to study different functional and anatomic features of the hyperplastic gland and clinical and biochemical characteristics of renal hyperparathyroidism (HPT) patients and their relationship with the scintigraphic detection of parathyroid glands. METHODS: A retrospective study was performed of 40 patients with chronic renal failure (CRF) who underwent cervical surgery for HPT. Weight, histology, and localization of hyperplastic glands were recorded. Parathyroid cell proliferation was assessed by percentage of S-phase cells. Double-phase scintigraphy with technetium 99m-sestamibi and serum parathyroid intact hormone (PTHi), creatinine, calcium, and phosphate levels were performed. RESULTS: Detection of hyperplastic parathyroid glands by 99mTc-sestamibi scintigraphy was associated with the weight and inferior localization of the glands. The functionality of the glands as reflected in serum PTHi and phosphorus levels was associated with the number of glands detected. CONCLUSION: Double-phase 99mTc-sestamibi scintigraphy is of limited usefulness in patients with renal HPT. Detection of hyperplastic parathyroid glands in patients with CRF depends on the weight and inferior localization of the glands. Serum PTHi, phosphorus and creatine levels are associated with the number of glands detected by means of 99mTc-sestamibi scintigraphy.