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Genetics of metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW) in children, and the childhood predictors of adulthood MHO and MUNW

Periodic Reporting for period 1 - Child-MHO (Genetics of metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW) in children, and the childhood predictors of adulthood MHO and MUNW)

Periodo di rendicontazione: 2018-04-01 al 2019-03-31

Recent large-scale genomic studies have provided evidence that a number of genetic variants implicate an inverse relationship
between increased adiposity and an unfavorable cardiometabolic profile. So far, it is not known whether the loci showing “favorable adiposity”-like
associations exert their influence already in childhood.Identification of genetic variation contributing to the link between adiposity and its complications in children and adolescents is important, as it could shed light on the underlying mechanisms and help distinguishing between the children who are most and least prone to developing cardiometabolic impairments upon weight gain. Furthemore, a present, it is not known whether early life factors also contribute to the development of MUNW. Identifying early predictors of MUNW could improve the identification of individuals at high risk and help develop appropriate interventions.


Identification of MHO and MUNW related genetic variants in children and the childhood predictors of adult MHO and MUNW will help to assess the risk of type 2 diabetes and cardiovascular disease as well as to target interventions in the high-risk groups. The ability to improve advice and intervention measures would help alleviate the burden of obesity-related comorbidities on health care systems worldwide.


In the present project, I examined which of the genetic determinants of MHO and MUNW found in adults are associated with “favorable adiposity”-like association patterns in children, and to detected childhood genetic and environmental predictors of adult MUNW. This novel and timely research has provided valuable information on the link between adiposity and its complications in childhood populations. This project has allowed me to learn highly valuable research skills in the area of genetics and meta-analyses related to cardiometabolic risk factors and support my
professional and research advancement.


The conclusion of the project are:
- genetic predisposition to higher body fat yet lower cardiometabolic risk (the so called MHO phenotype) as well as lower body fat yet higher cardiometabolic risk (MUNW) phenotype exerts its influence before puberty.
-Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood
- a relatively higher increase in BMI from childhood to adulthood, male sex, and lower childhood HDL cholesterol were the main early predictors for adult MUNW

These findings provide novel insights into the link between adiposity and its complications in children and adolescents.The results also highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with tendency for abdominal adiposity.Furthemore the results suggest that in individuals who remain normal weight, relatively higher increase in adiposity from childhood to adulthood is harmful to cardiometabolic health, and early adoption of a healthy lifestyle is thus critical.
"As planned, I worked 9 months (1 April 2018-31 December 2018) in Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism
Faculty of Health and Medical Sciences, University of Copenhagen under the supervision of associate professor Tuomas Kilpeläinen. After that I worked for three months (1 January 2019-31 March 2019) in Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland under the supervision of professor Olli Raitakari.


During the 9 months in Copenhagen, I analysed the data and wrote the manuscript of the first two articles called ""Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents"" (Figure 1) and ""Abdominal adiposity and cardiometabolic risk in children and adolescents; a Mendelian randomization analysis"" (Figure 2). I also started to work on the third article called ""Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults"" that I finished during the secondmend in Turku. During the secondment, I also made revisions of the first two articles to International Journal of Obesity and American Journal of Clinical Nutrition. The first article has been accepted by International Journal of Obesity. The second article is under review for the second round in American Journal of Clinical Nutrition. The third atricle has been submitted to International Jounal of Obesity.
The main result of the first article was that genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty (Figure 3).
The main results of the second article was that abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood (Figure 4).
The main result of the third article was that an increase in adiposity from childhood to adulthood is detrimental to cardiometabolic health, even among individuals remaining normal weight.


The results of this project will be published in high-impact international journals. The Marie Sklodowska-Curie actions have been mentioned in the articles. During the project, I took part in several group and section meetings, several workshops, thesis presentations, and conferences. I also gave oral and poster presentations in some of these gatherings addressed for both academic and/or non- (such as ""science and social meeting ""at the University of CPH, section meetings, ""End of the year event"" at University of CPH). I have also planned to present the resuts in conferences and meetings after the end of the project. Once the artciles are published, it has been planned that the resuls will be presented in the homepage of the Novo Nordisk Foundation Centre for Basic Metabolic Research and press releases sent. We have been interviewed about this project to CORDIS EU*Magazine by writer Thomas Bauwens and the arcile will be published soon."
The results of the project (untill the end of the project) have been presented above.
By finding ways for early prevention of obesity, type 2 diabetes and cardiovascular disease, which cause a growing economic burden worldwide, this project supports resource wise economy. The results of the project help distinguishing children who are most and least prone to developing cardiometabolic impairments upon weight gain. The results also highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with tendency for abdominal adiposity. The results also suggest that even in individuals who remain normal weight and particularly in men, relatively higher increase in adiposity from childhood to adulthood is harmful to cardiometabolic health, and early adoption of a healthy lifestyle is thus critical. These factors can help understanding which factors need to be taken into account when assessing an individual’s need for an early intervention.