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      Combatting type 2 diabetes by turning up the heat

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          Abstract

          In our westernised society, the level of physical activity is low. Interventions that increase energy expenditure are generally associated with an improvement in metabolic health. Exercise and exercise training increase energy metabolism and are considered to be among the best strategies for prevention of type 2 diabetes mellitus. More recently, cold exposure has been suggested to have a therapeutic value in type 2 diabetes. At a cellular level, there is evidence that increasing the turnover of cellular substrates such as fatty acids is associated with preventive effects against lipid-induced insulin resistance. Cellular energy sensors may underlie the effects linking energy turnover with metabolic health effects. Here we review data supporting the hypothesis that increasing energy and substrate turnover has beneficial effects on insulin sensitivity and should be considered a target for the prevention and treatment of type 2 diabetes.

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          The online version of this article (doi:10.1007/s00125-016-4068-3) contains a slideset of the figures for download, which is available to authorised users.

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          Breaks in sedentary time: beneficial associations with metabolic risk.

          Genevieve N Healy, David Dunstan, Jo Salmon … (2008)
          Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk. Participants (n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004-2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute(-1) or = 100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis. Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized beta = -0.16, 95% CI -0.31 to -0.02, P = 0.026), BMI (beta = -0.19, -0.35 to -0.02, P = 0.026), triglycerides (beta = -0.18, -0.34 to -0.02, P = 0.029), and 2-h plasma glucose (beta = -0.18, -0.34 to -0.02, P = 0.025). This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.
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            Sirtuins in mammals: insights into their biological function.

            Shaday Michan, David. Sinclair (2007)
            Sirtuins are a conserved family of proteins found in all domains of life. The first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces cerevisiae, from which the family derives its name, regulates ribosomal DNA recombination, gene silencing, DNA repair, chromosomal stability and longevity. Sir2 homologues also modulate lifespan in worms and flies, and may underlie the beneficial effects of caloric restriction, the only regimen that slows aging and extends lifespan of most classes of organism, including mammals. Sirtuins have gained considerable attention for their impact on mammalian physiology, since they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. In this review we describe our current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, and we will also discuss their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases.
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              Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans.

              Véronique Ouellet, Sébastien M. Labbé, Denis Blondin … (2012)
              Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.
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                Author and article information

                Contributors
                Patrick Schrauwen: p.schrauwen@maastrichtuniversity.nl
                Journal
                Journal ID (nlm-ta): Diabetologia
                Journal ID (iso-abbrev): Diabetologia
                Title: Diabetologia
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0012-186X
                ISSN (Electronic): 1432-0428
                Publication date (Electronic): 3 September 2016
                Publication date PMC-release: 3 September 2016
                Publication date (Print): 2016
                Volume: 59
                Issue: 11
                Pages: 2269-2279
                Affiliations
                GRID grid.412966.e, Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, , Maastricht University Medical Center, ; P.O. BOX 616, 6200MD Maastricht, the Netherlands
                Article
                Publisher ID: 4068
                DOI: 10.1007/s00125-016-4068-3
                PMC ID: 5506100
                PubMed ID: 27591854
                SO-VID: e1ba5cc8-15c3-447b-8c66-e74c0daa10da
                Copyright © © The Author(s) 2016
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 16 March 2016
                Date accepted : 22 June 2016
                Funding
                Funded by: Maastricht University
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © Springer-Verlag Berlin Heidelberg 2016

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: brown adipose tissue,cold-induced thermogenesis,diabetes,energy turnover,review
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: brown adipose tissue, cold-induced thermogenesis, diabetes, energy turnover, review

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