Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity
Klöting, N. et al. Insulin-sensitive obesity. Am. J. Physiol. Endocrinol. Metab. 299, E506–E515 (2010).
Google Scholar
Schleh, M. W. et al. Metabolic dysfunction in obesity is related to impaired suppression of fatty acid release from adipose tissue by insulin. Obesity 31, 1347–1361 (2023).
Google Scholar
Åkra, S. et al. Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men. Sci. Rep. 10, 14055 (2020).
Google Scholar
Sun, K., Kusminski, C. M. & Scherer, P. E. Adipose tissue remodeling and obesity. J. Clin. Invest. 121, 2094–2101 (2011).
Google Scholar
Sun, K., Tordjman, J., Clément, K. & Scherer, P. E. Fibrosis and adipose tissue dysfunction. Cell Metab. 18, 470–477 (2013).
Google Scholar
Clément, K. et al. Weight loss regulates inflammation‐related genes in white adipose tissue of obese subjects. FASEB J. 18, 1657–1669 (2004).
Google Scholar
McQuaid, S. E. et al. Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition? Diabetes 60, 47–55 (2011).
Google Scholar
Van Pelt, D. W., Guth, L. M. & Horowitz, J. F. Aerobic exercise elevates markers of angiogenesis and macrophage IL-6 gene expression in the subcutaneous adipose tissue of overweight-to-obese adults. J. Appl. Physiol. 123, 1150–1159 (2017).
Google Scholar
Riis, S. et al. Molecular adaptations in human subcutaneous adipose tissue after ten weeks of endurance exercise training in healthy males. J. Appl. Physiol. 126, 569–577 (2019).
Google Scholar
Fabre, O. et al. Exercise training alters the genomic response to acute exercise in human adipose tissue. Epigenomics 10, 1033–1050 (2018).
Google Scholar
Magkos, F. et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 23, 591–601 (2016).
Google Scholar
Cullberg, K. B. et al. Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects. Obesity 21, 454–460 (2013).
Google Scholar
Campbell, K. L. et al. Gene expression changes in adipose tissue with diet- and/or exercise-induced weight loss. Cancer Prev. Res. (Phila.) 6, 217–231 (2013).
Google Scholar
Ahn, C. et al. Exercise training remodels subcutaneous adipose tissue in adults with obesity even without weight loss. J. Physiol. 600, 2127–2146 (2022).
Google Scholar
Arner, E. et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59, 105–109 (2010).
Google Scholar
Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008).
Google Scholar
Christodoulides, C., Lagathu, C., Sethi, J. K. & Vidal-Puig, A. Adipogenesis and WNT signalling. Trends Endocrinol. Metab. 20, 16–24 (2009).
Google Scholar
Lowe, C. E., O’Rahilly, S. & Rochford, J. J. Adipogenesis at a glance. J. Cell Sci. 124, 2681–2686 (2011).
Google Scholar
Melincovici, C. S. et al. Vascular endothelial growth factor (VEGF) – key factor in normal and pathological angiogenesis. Rom. J. Morphol. Embryol. 59, 455–467 (2018).
Google Scholar
Hato, T., Tabata, M. & Oike, Y. The role of angiopoietin-like proteins in angiogenesis and metabolism. Trends Cardiovasc. Med. 18, 6–14 (2008).
Google Scholar
Khan, T. et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29, 1575–1591 (2009).
Google Scholar
Chun, T. H. et al. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell 125, 577–591 (2006).
Google Scholar
Chun, T.-H. et al. Genetic link between obesity and MMP14-dependent adipogenic collagen turnover. Diabetes 59, 2484–2494 (2010).
Google Scholar
Li, X. et al. Critical role of matrix metalloproteinase 14 in adipose tissue remodeling during obesity. Mol. Cell. Biol. 40, e00564-19 (2020).
Google Scholar
Bost, F., Aouadi, M., Caron, L. & Binétruy, B. The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51–56 (2005).
Google Scholar
Zewde, N., Gorham, R. D. Jr, Dorado, A. & Morikis, D. Quantitative modeling of the alternative pathway of the complement system. PLoS ONE 11, e0152337 (2016).
Google Scholar
Xiao, Y. et al. A novel significance score for gene selection and ranking. Bioinformatics 30, 801–807 (2012).
Google Scholar
Engeli, S. et al. Regulation of the nitric oxide system in human adipose tissue. J. Lipid Res. 45, 1640–1648 (2004).
Google Scholar
Halberg, N. et al. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29, 4467–4483 (2009).
Google Scholar
Lee, Y. S. et al. Increased adipocyte O2 consumption triggers HIF-1alpha, causing inflammation and insulin resistance in obesity. Cell 157, 1339–1352 (2014).
Google Scholar
Ridnour, L. A. et al. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc. Natl Acad. Sci. USA 102, 13147–13152 (2005).
Google Scholar
Walton, R. G. et al. Insulin‐resistant subjects have normal angiogenic response to aerobic exercise training in skeletal muscle, but not in adipose tissue. Physiol. Rep. 3, e12415 (2015).
Google Scholar
Čížková, T. et al. Exercise training reduces inflammation of adipose tissue in the elderly: cross-sectional and randomized interventional trial. J. Clin. Endocrinol. Metab. 105, e4510–e4526 (2020).
Google Scholar
Li, L. et al. Exercise retards ongoing adipose tissue fibrosis in diet-induced obese mice. Endocr. Connect. 10, 325–335 (2021).
Google Scholar
Huang, G. et al. α3(V) collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues. J. Clin. Invest. 121, 769–783 (2011).
Google Scholar
Pasarica, M. et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58, 718–725 (2009).
Google Scholar
Springer, N. L. et al. Obesity-associated extracellular matrix remodeling promotes a macrophage phenotype similar to tumor-associated macrophages. Am. J. Pathol. 189, 2019–2035 (2019).
Google Scholar
Spencer, M. et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am. J. Physiol. Endocrinol. Metab. 299, E1016–E1027 (2010).
Google Scholar
Henegar, C. et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 9, R14 (2008).
Google Scholar
Bruun, J. M., Helge, J. W., Richelsen, B. & Stallknecht, B. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am. J. Physiol. Endocrinol. Metab. 290, E961–E967 (2006).
Google Scholar
Dieli-Conwright, C. M. et al. Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention. Breast Cancer Res. Treat. 168, 147–157 (2018).
Google Scholar
Kawanishi, N., Yano, H., Yokogawa, Y. & Suzuki, K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc. Immunol. Rev. 16, 105–118 (2010).
Google Scholar
Kolahdouzi, S., Talebi-Garakani, E., Hamidian, G. & Safarzade, A. Exercise training prevents high-fat diet-induced adipose tissue remodeling by promoting capillary density and macrophage polarization. Life Sci. 220, 32–43 (2019).
Google Scholar
Mamane, Y. et al. The C3a anaphylatoxin receptor is a key mediator of insulin resistance and functions by modulating adipose tissue macrophage infiltration and activation. Diabetes 58, 2006–2017 (2009).
Google Scholar
Jia, Q., Morgan-Bathke, M. E. & Jensen, M. D. Adipose tissue macrophage burden, systemic inflammation, and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 319, E254–E264 (2020).
Google Scholar
Morgan-Bathke, M., Chen, L., Oberschneider, E., Harteneck, D. & Jensen, M. D. Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity. Am. J. Physiol. Endocrinol. Metab. 308, E830–E846 (2015).
Google Scholar
Shrago, E., Glennon, J. A. & Gordon, E. S. Comparative aspects of lipogenesis in mammalian tissues. Metabolism 20, 54–62 (1971).
Google Scholar
Ortega, F. J. et al. The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects. Obesity 18, 13–20 (2010).
Google Scholar
Diraison, F., Dusserre, E., Vidal, H., Sothier, M. & Beylot, M. Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity. Am. J. Physiol. Endocrinol. Metab. 282, E46–E51 (2002).
Google Scholar
Vijayakumar, A. et al. Absence of carbohydrate response element binding protein in adipocytes causes systemic insulin resistance and impairs glucose transport. Cell Rep. 21, 1021–1035 (2017).
Google Scholar
Cao, H. et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134, 933–944 (2008).
Google Scholar
Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014).
Google Scholar
Furukawa, S. et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752–1761 (2004).
Google Scholar
Rönn, T. et al. Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6‐month exercise intervention. Acta Physiol. (Oxf.) 211, 188–200 (2014).
Google Scholar
Townsend, L. K., Knuth, C. M. & Wright, D. C. Cycling our way to fit fat. Physiol. Rep. 5, e13247 (2017).
Google Scholar
Jornayvaz, F. R. & Shulman, G. I. Regulation of mitochondrial biogenesis. Essays Biochem. 47, 69–84 (2010).
Google Scholar
Nicholls, D. G. Hamster brown‐adipose‐tissue mitochondria: purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site. Eur. J. Biochem. 62, 223–228 (1976).
Google Scholar
Boström, P. et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012).
Google Scholar
Khalafi, M. et al. The impact of moderate-intensity continuous or high-intensity interval training on adipogenesis and browning of subcutaneous adipose tissue in obese male rats. Nutrients 12, 925 (2020).
Google Scholar
Tanimura, R., Kobayashi, L., Shirai, T. & Takemasa, T. Effects of exercise intensity on white adipose tissue browning and its regulatory signals in mice. Physiol. Rep. 10, e15205 (2022).
Google Scholar
Vosselman, M. et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int. J. Obes. 39, 1696–1702 (2015).
Google Scholar
Tsiloulis, T. et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int. J. Obes. 42, 721–727 (2018).
Google Scholar
Komili, S., Farny, N. G., Roth, F. P. & Silver, P. A. Functional specificity among ribosomal proteins regulates gene expression. Cell 131, 557–571 (2007).
Google Scholar
Song, G., Chen, J., Deng, Y., Sun, L. & Yan, Y. TMT labeling reveals the effects of exercises on the proteomic characteristics of the subcutaneous adipose tissue of growing high-fat-diet-fed rats. ACS Omega 8, 23484–23500 (2023).
Google Scholar
Robinson, M. M. et al. Enhanced protein translation underlies improved metabolic and physical adaptations to different exercise training modes in young and old humans. Cell Metab. 25, 581–592 (2017).
Google Scholar
Glisovic, T., Bachorik, J. L., Yong, J. & Dreyfuss, G. RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett. 582, 1977–1986 (2008).
Google Scholar
Louis, J. M., Agarwal, A., Aduri, R. & Talukdar, I. Global analysis of RNA–protein interactions in TNF‐α induced alternative splicing in metabolic disorders. FEBS Lett. 595, 476–490 (2021).
Google Scholar
Zhang, P. et al. RNA-binding proteins in the regulation of adipogenesis and adipose function. Cells 11, 2357 (2022).
Google Scholar
Muller, S. et al. Human adipose stromal–vascular fraction self-organizes to form vascularized adipose tissue in 3D cultures. Sci. Rep. 9, 7250 (2019).
Google Scholar
Hu, W. & Lazar, M. A. Modelling metabolic diseases and drug response using stem cells and organoids. Nat. Rev. Endocrinol. 18, 744–759 (2022).
Google Scholar
Hunter, A. L. et al. Adipocyte NR1D1 dictates adipose tissue expansion during obesity. eLife 10, e63324 (2021).
Google Scholar
Mendham, A. E. et al. Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function. Sci. Rep. 10, 3785 (2020).
Google Scholar
Short, K. R. et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes 52, 1888–1896 (2003).
Google Scholar
Prior, S. J. et al. Increased skeletal muscle capillarization independently enhances insulin sensitivity in older adults after exercise training and detraining. Diabetes 64, 3386–3395 (2015).
Google Scholar
Segal, K. R. et al. Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men. J. Appl. Physiol. 71, 2402–2411 (1991).
Google Scholar
Ross, R. et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial. Ann. Intern. Med. 133, 92–103 (2000).
Google Scholar
Morrison, D. J. et al. Measurement of postprandial glucose fluxes in response to acute and chronic endurance exercise in healthy humans. Am. J. Physiol. Endocrinol. Metab. 314, E503–E511 (2018).
Google Scholar
Ryan, B. J. et al. Moderate-intensity exercise and high-intensity interval training affect insulin sensitivity similarly in obese adults. J. Clin. Endocrinol. Metab. 105, e2941–e2959 (2020).
Google Scholar
Karastergiou, K., Smith, S. R., Greenberg, A. S. & Fried, S. K. Sex differences in human adipose tissues–the biology of pear shape. Biol. Sex Differ. 3, 13 (2012).
Google Scholar
Verboven, K. et al. Adrenergically and non-adrenergically mediated human adipose tissue lipolysis during acute exercise and exercise training. Clin. Sci. 132, 1685–1698 (2018).
Google Scholar
Godin, G. The Godin–Shephard Leisure-Time Physical Activity Questionnaire. Health Fit. J. Can. 4, 18–22 (2011).
Balke, B. & Ware, R. W. An experimental study of physical fitness of Air Force personnel. U.S. Armed Forces Med. J. 10, 675–688 (1959).
Google Scholar
Sieckmann, K. et al. AdipoQ—a simple, open-source software to quantify adipocyte morphology and function in tissues and in vitro. Mol. Biol. Cell 33, br22 (2022).
Google Scholar
McAlister, G. C. et al. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal. Chem. 86, 7150–7158 (2014).
Google Scholar
Wang, S. et al. NAguideR: performing and prioritizing missing value imputations for consistent bottom-up proteomic analyses. Nucleic Acids Res. 48, e83 (2020).
Google Scholar
Kuleshov, M. V. et al. KEA3: improved kinase enrichment analysis via data integration. Nucleic Acids Res. 49, W304–W316 (2021).
Google Scholar
Rojas-Rodriguez, R. et al. Adipose tissue angiogenesis assay. Methods Enzymol. 537, 75–91 (2014).
Google Scholar
Schmittgen, T. D. & Livak, K. J. Analyzing real-time PCR data by the comparative CT method. Nat. Protoc. 3, 1101–1108 (2008).
Google Scholar
Camastra, S. et al. Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery. Sci. Rep. 7, 9007 (2017).
Google Scholar
Acosta, J. R. et al. Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes. Diabetologia 59, 560–570 (2016).
Google Scholar
Ahn, C. & Horowitz, J. F. Years of endurance exercise training remodels abdominal subcutaneous adipose tissue in adults with overweight/obesity. Figshare (2024).
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