Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume.

OBJECTIVE: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans. METHODS: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 ± 2.3 y; 24.9 ± 5.1 kg/m2 ). BAT volume, 18 F-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure. RESULTS: Cold exposure increased the concentration of CXCL14 (Δ2h = 0.58 ± 0.98 ng/mL; p = 0.007), GDF15 (Δ2h = 19.63 ± 46.2 pg/mL; p = 0.013), FGF21 (Δ2h = 33.72 ± 55.13 pg/mL; p = 0.003), and IL6 (Δ1h = 1.98 ± 3.56 pg/mL; p = 0.048) and reduced BMP8b (Δ2h = -37.12 ± 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Δ2h: ß = 0.456; R2 = 0.307; p = 0.001), but not with 18 F-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity. CONCLUSIONS: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.

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.

Multidisciplinary Prehabilitation and Postoperative Rehabilitation for Avoiding Complications in Patients Undergoing Resection of Colon Cancer: Rationale, Design, and Methodology of the ONCOFIT Study.

ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary Prehabilitation and Postoperative Program (PPP) on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention (after 12 weeks) and 1-year post-surgery, and will include: post-surgery complications (primary endpoint); prolonged hospital length of stay; readmissions and emergency department call within 1-year after surgery; functional capacity; patient reported outcome measures targeted; anthropometry and body composition; clinical/tumor parameters; physical activity levels and sedentariness; dietary habits; other unhealthy habits; sleep quality; and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community, but also in clinical practice.

Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults.

OBJECTIVE: Omega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid-derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. METHODS: Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). RESULTS: Plasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress-derived 8,12-iso-iPF2α -VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals. CONCLUSION: Plasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.

Plasma Levels of Bile Acids Are Related to Cardiometabolic Risk Factors in Young Adults.

CONTEXT: Bile acids (BA) are known for their role in intestinal lipid absorption and can also play a role as signaling molecules to control energy metabolism. Prior evidence suggests that alterations in circulating BA levels and in the pool of circulating BA are linked to an increased risk of obesity and a higher incidence of type 2 diabetes in middle-aged adults. OBJECTIVE: We aimed to investigate the association between plasma levels of BA with cardiometabolic risk factors in a cohort of well-phenotyped, relatively healthy young adults. METHODS: Body composition, brown adipose tissue, serum classical cardiometabolic risk factors, and a set of 8 plasma BA (including glyco-conjugated forms) in 136 young adults (age 22.1 ± 2.2 years, 67% women) were measured. RESULTS: Plasma levels of chenodeoxycholic acid (CDCA) and glycoursodeoxycholic acid (GUDCA) were higher in men than in women, although these differences disappeared after adjusting for body fat percentage. Furthermore, cholic acid (CA), CDCA, deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA) levels were positively, yet weakly associated, with lean body mass (LBM) levels, while GDCA and glycolithocholic acid (GLCA) levels were negatively associated with 18F-fluorodeoxyglucose uptake by brown adipose tissue. Interestingly, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), and GUDCA were positively associated with glucose and insulin serum levels, HOMA index, low-density lipoprotein cholesterol, tumor necrosis factor alpha, interleukin (IL)-2, and IL-8 levels, but negatively associated with high-density lipoprotein cholesterol, ApoA1, and adiponectin levels, yet these significant correlations partially disappeared after the inclusion of LBM as a confounder. CONCLUSION: Our findings indicate that plasma levels of BA might be sex dependent and are associated with cardiometabolic and inflammatory risk factors in young and relatively healthy adults.

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.