Review Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis A. Sabag a,b , K.L. Way a,b , S.E. Keating a,c , R.N. Sultana b,d , H.T. O’Connor a , M.K. Baker b,d , V.H. Chuter e , J. George f , N.A. Johnson a,b, * a Faculty of Health Sciences, University of Sydney, NSW, Australia b Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia c Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, Queensland, Australia d School of Exercise Science, Australian Catholic University, NSW, Australia e School of Health Sciences, University of Newcastle, NSW, Australia f Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, NSW, Australia Introduction Overweight and obesity contributes to the increased world- wide prevalence of cardiovascular and metabolic morbidity and mortality [1]. Evidence also suggests that the location of excess adiposity, particularly that stored around the organs as visceral adipose tissue (VAT), is of greater importance in determining adverse health outcomes than the larger subcutaneous adipose tissue reserves [2]. More recently, excess adiposity within lean tissues has been associated with the underlying pathophysiologi- cal characteristics of type 2 diabetes. For instance, increased fat within the liver is associated with insulin resistance [3], impaired glycaemic control [4] and increased cardiovascular disease risk [2]. Similarly, small amounts of fat within muscle cells, the pancreas and myocardium and have been linked with peripheral insulin resistance [5], impaired insulin secretion [6] and hypertension/cardiomyopathy [7], respectively. Given the asso- ciation between these ‘‘ectopic fats’’ [8] and adverse metabolic and cardiovascular outcomes, it is important to determine the Diabetes & Metabolism xxx (2017) xxx–xxx A R T I C L E I N F O Article history: Received 7 October 2016 Received in revised form 11 November 2016 Accepted 7 December 2016 Available online xxx Keywords: Aerobic exercise Ectopic fat Hepatic fat Resistance training Visceral fat A B S T R A C T Ectopic adipose tissue surrounding the intra-abdominal organs (visceral fat) and located in the liver, heart, pancreas and muscle, is linked to cardio-metabolic complications commonly experienced in type 2 diabetes. A systematic review and meta-analysis was performed to determine the effect of exercise on ectopic fat in adults with type 2 diabetes. Relevant databases were searched to February 2016. Included were randomised controlled studies, which implemented  4 weeks of aerobic and/or resistance exercise and quantified ectopic fat via magnetic resonance imaging, computed tomography, proton magnetic resonance spectroscopy or muscle biopsy before and after intervention. Risk of bias and study quality was assessed using Egger’s funnel plot test and modified Downs and Black checklist, respectively. Of the 10,750 studies retrieved, 24 were included involving 1383 participants. No studies were found assessing the interaction between exercise and cardiac or pancreas fat. One study assessed the effect of exercise on intramyocellular triglyceride concentration. There was a significant pooled effect size for the meta-analysis comparing exercise vs. control on visceral adiposity (ES = 0.21, 95% CI: 0.37 to 0.05; P = 0.010) and a near-significant pooled effect size for liver steatosis reduction with exercise (ES = 0.28, 95% CI: 0.57 to 0.01; P = 0.054). Aerobic exercise (ES = 0.23, 95% CI: 0.44 to 0.03; P = 0.025) but not resistance training exercise (ES = 0.13, 95% CI: 0.37 to 0.12; P = 0.307) was effective for reducing visceral fat in overweight/obese adults with type 2 diabetes. These data suggest that exercise effectively reduces visceral and perhaps liver adipose tissue and that aerobic exercise should be a key feature of exercise programs aimed at reducing visceral fat in obesity-related type 2 diabetes. Further studies are required to assess the relative efficacy of exercise modality on liver fat reduction and the effect of exercise on pancreas, heart, and intramyocellular fat in type 2 diabetes and to clarify the effect of exercise on ectopic fat independent of weight loss.  C 2017 Elsevier Masson SAS. All rights reserved. * Corresponding author at: Discipline of Exercise and Sport Science, University of Sydney, Lidcombe, NSW, 2141, Australia. Tel.: +61 2 9351 9137; fax: +61 2 9351 9204. E-mail address: nathan.johnson@sydney.edu.au (N.A. Johnson). G Model DIABET-845; No. of Pages 16 Please cite this article in press as: Sabag A, et al. Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab (2017), http://dx.doi.org/10.1016/j.diabet.2016.12.006 Available online at ScienceDirect www.sciencedirect.com http://dx.doi.org/10.1016/j.diabet.2016.12.006 1262-3636/  C 2017 Elsevier Masson SAS. All rights reserved.