Gene analysis for studying the process of weight regain after weight loss Citation for published version (APA): Roumans, N. J. T. (2017). Gene analysis for studying the process of weight regain after weight loss. Gildeprint Drukkerijen. https://doi.org/10.26481/dis.20170623nr Document status and date: Published: 01/01/2017 DOI: 10.26481/dis.20170623nr Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.umlib.nl/taverne-license Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 04 Oct. 2021 Gene analysis for studying the process of weight regain after weight loss The studies presented in this thesis were performed within NUTRIM School for Nutrition and Translational Research in Metabolism, which participates in the Graduate School VLAG (Food Technology, Agrobiotechnology, Nutrition and Health Sciences), accredited by the Royal Netherlands Academy of Arts and Sciences. The studies described in this thesis were supported by a grant from Netherlands Organisation for Scientific Research (NWO) TOP, grant number: 200500001. Cover design: Nadia J.T. Roumans and Evelien Jagtman (http://evelienjagtman.com/) Layout: Nadia J.T. Roumans Printed by: Gildeprint – www.gildeprint.nl © Nadia J.T. Roumans, Maastricht 2016 For articles published or accepted for publication, the copyright has been transferred to the respective publisher. No parts of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without the permission of the author, or, when appropriate, from the publishers of the manuscript. Gene analysis for studying the process of weight regain after weight loss PROEFSCHRIFT ter verkrijging van de graad doctor aan de Universiteit Maastricht, op gezag van de Rector Magnificus, Prof. dr. Rianne M. Letschert, volgens het besluit van het College van Decanen, in het openbaar te verdedigen op vrijdag 23 Juni 2017 om 10.00 uur door Nadia Johanna Theodora Roumans Geboren te Zeven in Duitsland op 3 Maart 1989 Promotoren Prof. dr. E.C.M. Mariman Prof. dr. M.A. van Baak Beoordelingscommissie Prof. dr. E.E. Blaak, voorzitter Prof. dr. I.C. Arts Prof. dr. A.H. Kersten (Wageningen University & Research) Dr. E.M. van Schothorst (Wageningen University & Research) Prof. dr. L.P.A.J. Schrauwen Financiële ondersteuning Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO): TOP grant 200500001 Content Chapter 1 General introduction 7 Chapter 2 Variation in extracellular matrix genes is associated with weight 17 regain after weight loss in a sex-specific manner Chapter 3 A role for leukocyte and ECM remodelling of adipose tissue in 39 the risk for weight regain after weight loss Chapter 4 Weight loss-induced stress in subcutaneous adipose tissue is 65 related to weight regain Chapter 5 Weight loss-induced cellular stress in subcutaneous adipose 87 tissue and the risk for weight regain in overweight and obese adults Chapter 6 Relation between stress- and ECM-related genes and their 113 effect on weight regain Chapter 7 General discussion 145 Addendum Summary 157 Samenvatting 161 Valorization 167 Dankwoord/Acknowledgements 173 Curriculum Vitae 177 List of Publications 181 Chapter 1 General introduction 7 Chapter 1 Obesity The prevalence of overweight and obesity has increased worldwide, presenting major health problems (1). In 2014, the World Health Organization estimated that of adults aged 18 and over, 39% were overweight and 13% were obese (2). The prevalence of overweight and obesity is assessed by using body mass index (BMI), which is defined as weight in kilograms divided by the square of height in meters (kg/m2). Individuals with a BMI≥25 kg/m2 are classified as overweight and individuals with a BMI≥30 kg/m2 are classified as obese. The increasing prevalence of obesity is a major health concern since it increases the risk for developing type 2 diabetes mellitus (3), cardiovascular diseases (4) and certain types of cancer (5). In fact, overweight- and obesity-related health problems were estimated to cause 3.4 million deaths in 2010 (1). Overweight and obesity occur when there is a disturbance in the energy balance, which is determined by energy intake and expenditure. When energy balance is maintained, energy intake and energy expenditure are equal (Figure 1). If energy intake exceeds energy expenditure, the excessive energy is stored as triglycerides (TG) in the white adipose tissue (WAT). This causes weight gain and eventually obesity. On the other hand, if energy expenditure exceeds energy intake, the stored TG are used as fuel for other energy demanding processes elsewhere in the body. Figure 1: Balance between energy intake and energy expenditure. Nowadays the often-observed energy imbalance is mainly caused by the combination of a high calorie intake and a low physical activity (6). In our modern society, food is abundantly available and is also energy dense whereas the demand of physical activity is strongly reduced. However, this ‘obesogenic’ environment cannot fully explain the development of obesity at an individual level, since many people seem to be protected against obesity. This raises the question which factors determine the individual susceptibility to become obese. There is evidence that an individual’s susceptibility for gaining weight is determined in part by genetics (7, 8). Numerous genes have been identified that are associated with obesity (9). Genetic variants or single nucleotide polymorphisms (SNPs), like the polymorphism in the fat mass and obesity-associated (FTO) gene, have been linked to obesity (10-12). An individual with a genetic predisposition is unlikely to develop obesity without being exposed to an obesity-promoting environment, suggesting gene-environment interaction effects (13). For example, the body weight development of children is influenced by the BMI of their parents. A higher BMI for the parent is linked to a higher BMI in their children (14). This parental association is due to the combination of a shared genetic background and a shared lifestyle. Besides genetics, other factors also contribute to the individual’s susceptibility to become obese, such as aging: when people become older they tend to gain weight (15). Also, social, cultural and economic status, and inadequate sleep are associated with the prevalence of obesity (8, 16, 17). 8 General introduction Weight loss and weight regain There is a simple remedy to obesity, i.e. losing weight by limiting energy/food intake and increasing daily physical activity for a longer period of time. A body weight reduction of 5-10% reduces disease risk and improves the metabolic profile resulting in positive health outcomes (18, 19). However, the greatest challenge is the seemingly inevitable weight regain after weight loss, the so-called “yoyo- effect”. In general up to 80% of the people are unsuccessful in maintaining weight loss (20, 21) defined as “keeping off an intentional loss of at least 10% body weight for at least one year” (22). On average about 70% of the lost weight is regained within two years after the dietary intervention (23). Still, some individuals are able to keep off their lost weight, pointing to an individual susceptibility for weight maintenance or weight regain. Similarly to the predisposition to develop overweight or obesity, the individual susceptibility to successful weight loss and weight maintenance seems to be determined by multiple factors. Genetic, behavioural and physiological factors related to body weight might directly or indirectly affect weight loss and weight maintenance. Hormonal and genetic factors change in response to weight loss, thereby either changing to a pre-obese state or favouring weight regain. For instance, circulating mediators of appetite that enhance weight regain did not return to pre-weight loss levels one year after the start of the weight loss intervention (24). In addition, during weight loss circulating leptin concentrations decrease which could lead to