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... Show moreObjective: 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/m(2)). BAT volume, F-18-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 (Delta 2h = 0.58 +/- 0.98 ng/mL; p = 0.007), GDF15 (Delta 2h = 19.63 +/- 46.2 pg/mL; p = 0.013), FGF21 (Delta 2h = 33.72 +/- 55.13 pg/mL; p = 0.003), and IL6 (Delta 1h = 1.98 +/- 3.56 pg/mL; p = 0.048) and reduced BMP8b (Delta 2h = -37.12 +/- 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Delta 2h: beta = 0.456; R-2 = 0.307; p = 0.001), but not with F-18-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. Show less
Loh, N.Y.; Rosoff, D.; Noordam, R.; Christodoulides, C. 2023
ObjectiveThis study aimed to investigate whether independent dimensions of metabolic syndrome (MetS) components are associated differentially with incident cardiometabolic diseases.... Show moreObjectiveThis study aimed to investigate whether independent dimensions of metabolic syndrome (MetS) components are associated differentially with incident cardiometabolic diseases. MethodsPrincipal components analysis was performed using the five MetS components from 153,073 unrelated European-ancestry participants (55% women) from the UK Biobank. The associations of the principal components (PCs) with incident type 2 diabetes mellitus (T2D), coronary artery disease (CAD), and (ischemic) stroke were analyzed using multivariable-adjusted Cox proportional hazards models in groups stratified by sex and baseline age. ResultsPC1 (40.5% explained variance; increased waist circumference with dyslipidemia) and PC2 (22.7% explained variance; hyperglycemia) were both associated with incident cardiometabolic disease. Hazard ratios (HR [95% CI]) for CAD and T2D were higher for PC1 than for PC2 (1.27 [95% CI: 1.25-1.29] vs. 1.06 [95% CI: 1.03-1.08] and 2.09 [95% CI: 2.03-2.16] vs. 1.39 [95% CI: 1.34-1.44], respectively). Furthermore, the association of PC1 with T2D was slightly higher for women than for men, and especially the HRs of PC1 with CAD and T2D attenuated with increasing age (p values for heterogeneity test among subgroups < 0.05). ConclusionsMetS can be dissected into two distinct presentations characterized by differential sex- and age-associated cardiometabolic disease risk, confirming the loss of information using the dichotomous MetS. Show less
Egmond, L.T. van; Meth, E.M.S.; Engstrom, J.; Ilemosoglou, M.; Keller, J.A.; Vogel, H.; Benedict, C. 2022
ObjectiveThis study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. MethodsA total... Show moreObjectiveThis study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. MethodsA total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. ResultsAfter sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] mu g/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. ConclusionsAcute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation. Show less
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... Show moreObjective 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-iPF(2 alpha)-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. Show less
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... Show moreObjective 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-iPF(2 alpha)-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. Show less
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... Show moreObjective 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-iPF(2 alpha)-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. Show less
Objective Obesity is becoming a global public health problem, but it is unclear how it impacts different generations over the life course. Here, a descriptive analysis of the age-related changes in... Show moreObjective Obesity is becoming a global public health problem, but it is unclear how it impacts different generations over the life course. Here, a descriptive analysis of the age-related changes in anthropometric measures and related cardiometabolic risk factors across different generations was performed. Methods The development of anthropometric measures and related cardiometabolic risk factors was studied during 26 years of follow-up in the Doetinchem Cohort Study (N = 6,314 at baseline). All analyses were stratified by sex and generation, i.e., 10-year age groups (20-29, 30-39, 40-49, and 50-59 years) at baseline. Generalized estimating equations were used to test for generational differences. Results Weight, BMI, waist circumference, and prevalence of overweight and obesity were higher, in general, in the younger generations during the first 10 to 15 years of follow-up. From age 50 to 59 years onward, these measures converged in all generations of men and women. Among cardiometabolic risk factors, only type 2 diabetes showed an unfavorable shift between the two oldest generations of men. Conclusions It was observed that, compared with the older generations, the younger generations had obesity at an earlier age but did not reach higher levels at midlife and beyond. This increased exposure to obesity was not (yet) associated with increased prevalence of cardiometabolic risk factors. Show less
Velden, A.I.M. van der; Berg, B.M. van den; Mutsert, R. de; Vlag, J. van der; Jukema, J.W.; Rosendaal, F.R.; ... ; Vink, H. 2021
Objective This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease. Methods In this cross-sectional Netherlands... Show moreObjective This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease. Methods In this cross-sectional Netherlands Epidemiology of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4-7 mu m) and feed vessels (>10 mu m). Framingham Risk Score was used to calculate 10-year cardiovascular risk, divided into low-, intermediate-, and high-risk groups. ANOVA was used to evaluate microvascular differences among the groups. Results A total of 813 participants were included. The high-risk group (n = 168) was characterized by differences in the microvasculature compared with the low-risk group (n = 392): the high-risk group had a 49% reduction in the number of smallest capillaries and a 9.1-mu m/s (95% CI: 5.2-12.9) higher red blood cell velocity in the feed vessels. No differences in velocity-corrected perfused boundary regions were found. Conclusions It was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease. Show less
Objectives This study aimed to determine the effect of bariatric surgery-induced weight loss on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in postmenopausal, nondiabetic women... Show moreObjectives This study aimed to determine the effect of bariatric surgery-induced weight loss on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in postmenopausal, nondiabetic women.Methods A total of 14 postmenopausal, nondiabetic women with obesity who were scheduled for laparoscopic Roux-en-Y gastric bypass surgery (RYGB) were included in this study. Vertebral bone marrow fat signal fraction was determined by quantitative chemical shift magnetic resonance imaging, and vertebral volumetric BMD (vBMD) was determined by quantitative computed tomography before surgery and 3 and 12 months after surgery. Data were analyzed by linear mixed model.Results Body weight [mean (SD)] decreased after surgery from 108 (13) kg at baseline to 89 (12) kg at 3 months and 74 (11) kg at 12 months (P < 0.001). BMAT decreased after surgery from 51% (8%) at baseline to 50% (8%) at 3 months and 46% (7%) at 12 months (P = 0.004). vBMD decreased after surgery from 101 (26) mg/cm(3) at baseline to 94 (28) mg/cm(3) at 3 months (P = 0.003) and 94 (28) mg/cm(3) at 12 months (P = 0.035). Changes in BMAT and vBMD were not correlated (rho = -0.10 and P = 0.75). Calcium and vitamin D concentrations did not change after surgery.Conclusions RYGB decreases both BMAT (after 12 months) and vBMD (both after 3 months and 12 months) in postmenopausal, nondiabetic women. Changes in BMAT and vBMD were not correlated. These findings suggest that BMAT does not contribute to bone loss following RYGB. Show less
Objective This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. Methods Two... Show moreObjective This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. Methods Two different groups of 44 (study 1: 22.1 [SD 2.1] years old, 25.6 [SD 5.2] kg/m(2), 34% men) and 13 young healthy adults (study 2: 25.6 [SD 3.0] years old, 23.6 [SD 2.4] kg/m(2), 54% men) participated in this study. Resting metabolic rate (RMR) and macronutrient oxidation rates were measured by indirect calorimetry under fasting conditions in a warm environment (for 30 minutes) and in mild cold conditions (for 65 minutes, with the individual wearing a water-perfused cooling vest set at an individualized temperature adjusted to the individual's shivering threshold). Results In study 1, EE increased in the initial stage of cold exposure and remained stable for the whole cold exposure (P < 0.001). Mean cold-induced thermogenesis (9.56 +/- 7.9 kcal/h) was 13.9% +/- 11.6% of the RMR (range: -14.8% to 39.9% of the RMR). Carbohydrate oxidation decreased during the first 30 minutes of the cold exposure and later recovered up to the baseline values (P < 0.01) in parallel to opposite changes in fat oxidation (P < 0.01). Results were replicated in study 2. Conclusions A 1-hour mild cold exposure individually adjusted to elicit maximum nonshivering thermogenesis induces a very modest increase in EE and a shift of macronutrient oxidation that may underlie a shift in thermogenic tissue activity. Show less
Objective Exercise has been shown to improve cardiometabolic health, yet neither the molecular connection nor the effects of exercise timing have been elucidated. The aim of this study was to... Show moreObjective Exercise has been shown to improve cardiometabolic health, yet neither the molecular connection nor the effects of exercise timing have been elucidated. The aim of this study was to investigate whether ad libitum or time-restricted mild exercise reduces atherosclerosis development in atherosclerosis-prone dyslipidemic APOE*3-Leiden.CETP mice and whether mild exercise training in men with obesity affects lipoprotein levels. Methods Mice were group-housed and subjected to ad libitum or time-restricted (first or last 6 hours of the active phase) voluntary wheel running for 16 weeks while on a cholesterol-rich diet, after which atherosclerosis development was assessed in the aortic root. Furthermore, nine men with obesity followed a 12-week mild exercise training program. Lipoprotein levels were measured by nuclear magnetic resonance spectroscopy in plasma collected pre and post exercise training. Results Wheel running did not affect plasma lipid levels, uptake of triglyceride-derived fatty acids by tissues, and aortic atherosclerotic lesion size or severity. Markers of training status were unaltered. Exercise training in men with obesity did not alter lipoprotein levels. Conclusions Mild exercise training does not reduce dyslipidemia or atherosclerosis development in APOE*3-Leiden.CETP mice or affect lipoprotein levels in humans. Future research on the effects of (time-restricted) exercise on atherosclerosis or lipid metabolism should consider more vigorous exercise protocols. Show less
Objective Brown adipose tissue (BAT) is a thermogenic tissue with potential as a therapeutic target in the treatment of obesity and related metabolic disorders. The most used technique for... Show moreObjective Brown adipose tissue (BAT) is a thermogenic tissue with potential as a therapeutic target in the treatment of obesity and related metabolic disorders. The most used technique for quantifying human BAT activity is the measurement of F-18-fluorodeoxyglucose uptake via a positron emission tomography/computed tomography scan following exposure to cold. However, several studies have indicated the measurement of the supraclavicular skin temperature (SST) by infrared thermography (IRT) to be a less invasive alternative. This work reviews the state of the art of this latter method as a means of determining BAT activity in humans. Methods The data sources for this review were PubMed, Web of Science, and EBSCOhost (SPORTdiscus), and eligible studies were those conducted in humans. Results In most studies in which participants were first cooled, an increase in IRT-measured SST was noted. However, only 5 of 24 such studies also involved a nuclear technique that confirmed increased activity in BAT, and only 2 took into account the thickness of the fat layer when measuring SST by IRT. Conclusions More work is needed to understand the involvement of tissues other than BAT in determining IRT-measured SST; at present, IRT cannot determine whether any increase in SST is due to increased BAT activity. Show less
Objective This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and... Show moreObjective This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and wrist skin temperature (WT). Moreover, we examined whether BAT and skeletal muscle have a mediating role between Personal-ET and WT (as a proxy of peripheral vasoconstriction/vasodilation). Methods The levels of BAT were quantified by cold-induced F-18-fluorodeoxyglucose-positron emission tomography/computed tomography scan and measured the Personal-ET and WT by using iButtons (Maxim Integrated, Dallas, Texas) in 75 participants (74.6% women). Results The study found that BAT volume and metabolic activity played a positive and significant role (up to 25.4%) in the association between Personal-ET and WT. In addition, at the coldest temperatures, the participants with lower levels of WT (inducing higher peripheral vasoconstriction) had higher levels of BAT outcomes, whereas in warm temperatures, participants with higher levels of WT (inducing higher peripheral vasodilation) had lower levels of BAT outcomes. The study did not find any mediating role of skeletal muscle activity. Conclusions BAT volume and metabolic activity play a role in the relationship between Personal-ET and WT. Moreover, the data suggest that there are two distinct phenotypes: individuals who respond better to the cold, both through nonshivering thermogenesis and peripheral vasoconstriction, and individuals who respond better to the heat. Show less
Dekker, S.A.; Noordam, R.; Biermasz, N.R.; Roos, A. de; Lamb, H.J.; Rosendaal, F.R.; ... ; Mutsert, R. de 2018
The study aimed to investigate whether markers of endocannabinoid signaling differed between men with overweight of South Asian and white Caucasian descent. We included South Asian (n = 10) and... Show moreThe study aimed to investigate whether markers of endocannabinoid signaling differed between men with overweight of South Asian and white Caucasian descent. We included South Asian (n = 10) and white Caucasian (n = 10) men with overweight and prediabetes aged 35 to 50 years. Plasma samples were analyzed for endocannabinoids, their congeners, and lipids. In white adipose tissue (WAT) and skeletal muscle biopsies, mRNA expression of genes involved in the endocannabinoid system (ECS) was assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fasting lipid oxidation and glucose oxidation were determined with indirect calorimetry. was 10-fold lower (P < 0.001) and that of the endocannabinoid degradation enzyme fatty acid amide hydrolase 2 (FAAH2) was 5-fold lower (P < 0.001) compared to white Caucasians. Expression of genes involved in the ECS in WAT were not different between the two ethnicities. After pooling of both ethnicities, plasma 2-arachidonoylglycerol (2-AG) positively correlated with plasma triglycerides (R = 0.77, P < 0.001) and lipid oxidation (R = 0.55, P < 0.05). South Asian men with overweight have higher plasma 2-linoleoyl glycerol and N-linoleoylethanolamine levels and lower expression of CB receptors and the endocannabinoid degradation enzyme FAAH2 in skeletal muscle compared to white Caucasians. OBJECTIVE METHODS RESULTS CONCLUSIONS Show less
