13 research outputs found

    Human white-fat thermogenesis: Experimental and meta-analytic findings

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    © 2020 The Authors. Published by Taylor & Francis. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/23328940.2020.1769530White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low Tenv on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUVmax, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. Abbreviations: WAT:White adipose tissue; Tenv: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; 18F-FDG: F18 fludeoxyglucose; VO2peak:Peak oxygen consumption; 1RM: One repetition maximum; SUVmax: Maximum standardized uptake value; Std: Standardized mean difference.This work was supported by funding from the European Union 7th Framework Program FP7-PEOPLE-2012-IRSES grant no. [319010]; FP7-PEOPLE-2013-IRSES grant no. [612547] and Horizon 2020 ICI-THROUGH grant no [645710].Published versio

    Thermogenic capacity of human white-fat: the actual picture

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    Presented at the 9th Greek Conference of Biochemistry and Physiology of Exercise, Thessaloniki, Greece, 18–20 October 2019Cold exposure and exercise may increase thermogenic capacity of white adipose tissue (WAT), which could subsequently enhance energy expenditure and body weight loss. We aimed to identify possible alterations in uncoupling protein 1 (UCP1)—the main biomarker of thermogenic activation—in human WAT due to both cold exposure and exercise, as well as the link between environmental temperature and thermogenic capacity of human WAT. MATERIAL & METHOD: We conducted four human experimental studies and two systematic reviews and meta-analyses—PROSPERO registration CRD42019120116, CRD42019120213. RESULTS: UCP1 mRNA was higher in winter than in summer [t(30) = 2.232, p = 0.03] in human WAT and our meta-analysis showed a main effect of cold exposure on human UCP1 mRNA [standard mean difference (Std-md) = 1.81, confidence interval (CI) = 0.50–3.13, p = 0.007]. However, UCP1 mRNA/protein expressions displayed no associations with %fat mass or BMI (p > 0.05, Cohen’s f2 < 0.20). Both a 2-hour cooling and a non-cooling protocol preceding the positron emission tomography/computed tomography (PET/CT) measurements revealed no association between environmental temperature and standardised uptake value (SUVmax) of human WAT, as well as no mean differences in SUVmax-WAT-activity between winter and summer. An 8-week exercise program had no effect on UCP1 of human WAT or on body composition. Our meta-analysis also revealed: (a) no effect of chronic exercise on human UCP1 mRNA, (b) a main effect of chronic exercise on UCP1 protein concentrations (Std-md = 0.59, CI = 0.03–1.16, p = 0.04) and UCP1 mRNA (Std-md = 1.76, CI = 0.48–3.04, p = 0.007) in WAT of normal diet animals, c) a main effect of chronic exercise on UCP1 mRNA (Std-md = 2.94, CI = 0.24–5.65, p = 0.03) and UCP1 protein concentrations (Std-md = 2.06, CI = 0.07–4.05, p = 0.04) of high-fat diet animals. CONCLUSIONS: Cold exposure represents a main stimulus for increased thermogenic capacity in human white adipocytes; however, this may have no impact on body weight loss. Chronic exercise may represent no major stimulus for UCP1 induced in human white adipocytes, while in animals it increases UCP1 gene independently of their diet. Therefore, evidence from animal studies regarding UCP1 gene activation in white adipocytes may not be applicable in humans. Finally, the identification of human WAT thermogenic capacity via PET/CT examination may be optimal with both a cooling and a non-cooling protocol.Published onlin

    Characteristics of the Protocols Used in Electrical Pulse Stimulation of Cultured Cells for Mimicking In Vivo Exercise: A Systematic Review, Meta-Analysis, and Meta-Regression

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    While exercise benefits a wide spectrum of diseases and affects most tissues and organs, many aspects of its underlying mechanistic effects remain unsolved. In vitro exercise, mimicking neuronal signals leading to muscle contraction in vitro, can be a valuable tool to address this issue. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis, we searched EMBASE and PubMed (from database inception to 4 February 2022) for relevant studies assessing in vitro exercise using electrical pulse stimulation to mimic exercise. Meta-analyses of mean differences and meta-regression analyses were conducted. Of 985 reports identified, 41 were eligible for analysis. We observed variability among existing protocols of in vitro exercise and heterogeneity among protocols of the same type of exercise. Our analyses showed that AMPK, Akt, IL-6, and PGC1a levels and glucose uptake increased in stimulated compared to non-stimulated cells, following the patterns of in vivo exercise, and that these effects correlated with the duration of stimulation. We conclude that in vitro exercise follows motifs of exercise in humans, allowing biological parameters, such as the aforementioned, to be valuable tools in defining the types of in vitro exercise. It might be useful in transferring obtained knowledge to human research. © 2022 by the authors

    Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

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    Background: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis. Methods: Here we analyzed the effects of irisin on the metabolic activity of 3T3-L1 derived adipocytes through a mitochondrial flux assay. We also assessed the effects of irisin on the intracellular signaling through Western Blot. Finally, the gene expression of ucp1 and lipolytic genes was examined through RT-qPCR. Results: Irisin affects mitochondrial respiration and lipolysis in a time-dependent manner through the regulation of PI3K-AKT pathway. Irisin also induces the expression of UCP1 and the regulation of NF-κB, and CREB and ERK pathways. Conclusion: Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes. General significance: Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders. © 202

    Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

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    Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration. © 2022 by the authors

    Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

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    Background: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis. Methods: Here we analyzed the effects of irisin on the metabolic activity of 3T3-L1 derived adipocytes through a mitochondrial flux assay. We also assessed the effects of irisin on the intracellular signaling through Western Blot. Finally, the gene expression of ucp1 and lipolytic genes was examined through RT-qPCR. Results: Irisin affects mitochondrial respiration and lipolysis in a time-dependent manner through the regulation of PI3K-AKT pathway. Irisin also induces the expression of UCP1 and the regulation of NF-κB, and CREB and ERK pathways. Conclusion: Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes. General significance: Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders

    Effects of in vitro muscle contraction on thermogenic protein levels in co-cultured adipocytes

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    The crosstalk between the exercising muscle and the adipose tissue, mediated by myokines and metabolites, derived from both tissues during exercise has created a controversy between animal and human studies with respect to the impact of exercise on the browning process. The aim of this study was to investigate whether co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of electrical pulse stimulation (EPS) mimicking muscle contraction can impact the expression of UCP1, PGC-1a, and IL-6 in adipocytes, therefore providing evidence on the direct crosstalk between adipocytes and stimulated muscle cells. In the co-cultured C2C12 cells, EPS increased the expression of PGC-1a (p = 0.129; d = 0.73) and IL-6 (p = 0.09; d = 1.13) protein levels. When EPS was applied, we found that co-culturing led to increases in UCP1 (p = 0.044; d = 1.29) and IL-6 (p = 0.097; d = 1.13) protein expression in the 3T3-L1 adipocytes. The expression of PGC-1a increased by EPS but was not significantly elevated after co-culturing (p = 0.448; d = 0.08). In vitro co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of EPS leads to increased expression of thermogenic proteins. These findings indicate changes in the expression pattern of proteins related to browning of adipose tissue, supporting the use of this in vitro model to study the crosstalk between adipocytes and contracting muscle. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

    Association of fat mass profile with natriuretic peptide receptor alpha in subcutaneous adipose tissue of medication-free healthy men: A cross-sectional study

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    Background: Atrial natriuretic peptide increases lipolysis in human adipocytes by binding to natriuretic peptide receptor-A (NPRA). The aim of the current study was to examine the associations of NPRA mRNA of subcutaneous adipose tissue with fat mass, fat-free mass, body mass index (BMI) and arterial blood pressure in medication-free healthy men. Method: Thirty-two volunteers [age (years): 36.067.36, BMI: 27.604.63 (kg/m 2)] underwent assessments of body height/weight, % fat mass, fat-free mass (kg), blood pressure, and a subcutaneous adipose tissue biopsy via a surgical technique. Results: We found that NPRA mRNA was negatively associated with % fat mass (r=-0.40, R 2=0.16, p=0.03) and BMI (r=-0.45, R 2=0.20, p=0.01). Cohen's f 2 effect size analyses showed a small effect size between NPRA mRNA and BMI ( f 2 =0.25). One-way analysis of variance with Bonferroni post-hoc tests showed a tendency for mean differences of NPRA mRNA across BMI categories (p=0.06). This was confirmed by Cohen's d effect size analyses revealing a large effect size of NPRA mRNA between obese individuals (BMI≥30 kg/m 2) and either normal weight (BMI=19-25 kg/m 2; d=0.94) or overweight (BMI=25-30 kg/m 2; d=1.12) individuals. Conclusions: NPRA mRNA is negatively associated with % fat mass and BMI in medication-free healthy men, suggesting a possible role of NPRA in the control of fat mass accumulation. © 2018 Dinas PC et al

    Indicators to assess physiological heat strain–Part 3: Multi-country field evaluation and consensus recommendations

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    In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this third paper, we conducted field experiments across nine countries to evaluate the efficacy of 61 meteorology-based TSIs for assessing the physiological strain experienced by individuals working in the heat. We monitored 372 experi-enced and acclimatized workers during 893 full work shifts. We continuously assessed core body temperature, mean skin temperature, and heart rate data together with pre/post urine specific gravity and color. The TSIs were evaluated against 17 published criteria covering physiological parameters, practicality, cost effectiveness, and health guidance issues. Simple meteorological parameters explained only a fraction of the variance in physiological heat strain (R2 = 0.016 to 0.427; p < 0.001), reflecting the importance of adopting more sophisticated TSIs. Nearly all TSIs correlated with mean skin temperature (98%), mean body temperature (97%), and heart rate (92%), while 66% of TSIs correlated with the magnitude of dehydration and 59% correlated with core body temperature (r = 0.031 to 0.602; p < 0.05). When evaluated against the 17 published criteria, the TSIs scored from 4.7 to 55.4% (max score = 100%). The indoor (55.4%) and outdoor (55.1%) Wet-Bulb Globe Temperature and the Universal Thermal Climate Index (51.7%) scored higher compared to other TSIs (4.7 to 42.0%). Therefore, these three TSIs have the highest potential to assess the physiological strain experienced by individuals working in the heat. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

    Occupational heat stress: Multi-country observations and interventions

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    Background: Occupational heat exposure can provoke health problems that increase the risk of certain diseases and affect workers’ ability to maintain healthy and productive lives. This study investigates the effects of occupational heat stress on workers’ physiological strain and labor productivity, as well as examining multiple interventions to mitigate the problem. Methods: We monitored 518 full work-shifts obtained from 238 experienced and acclimatized individuals who work in key industrial sectors located in Cyprus, Greece, Qatar, and Spain. Continuous core body temperature, mean skin temperature, heart rate, and labor productivity were collected from the beginning to the end of all work-shifts. Results: In workplaces where self-pacing is not feasible or very limited, we found that occupational heat stress is associated with the heat strain experienced by workers. Strategies focusing on hydration, work-rest cycles, and ventilated clothing were able to mitigate the physiological heat strain experienced by workers. Increasing mechanization enhanced labor productivity without increasing workers’ physiological strain. Conclusions: Empowering la-borers to self-pace is the basis of heat mitigation, while tailored strategies focusing on hydration, work-rest cycles, ventilated garments, and mechanization can further reduce the physiological heat strain experienced by workers under certain conditions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
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