EASO New Investigators United Award Winner: Spotlight on Sini Heinonen

sini-heinonen-1Hello Sini. It’s great to have the opportunity to interview you.  Please tell us a bit about yourself.

I grew up in Tapiola, near Helsinki, the capital of Finland. Tapiola is a garden city with a very peaceful atmosphere, and I had a secure and happy childhood with my family which included both parents and a brother. Although I was interested in almost every subject at school, the most excited I got about subjects related to science; mathematics, physics, chemistry, biology, astronomy and geography. These subjects opened up a whole new world to me, and provided new realms to explore. As a child, I also read a lot of science magazines. I completedhigh-school with top grades and after graduation I began study at the University of Technology in physics, chemistry, mathematics and other life sciences. At that time, I also started a two-year professional education in the Finnish National Opera Ballet School in order to become a professional ballet dancer. I had actively danced since childhood and wanted to try dance at a professional level for a few years. During the next five years I studied part-time and danced professionally, both in the Finnish National Ballet and across Europe.  

In high school I was interested in medicine and medical research, partly due to my dance background and also because it seemed to combine mathematics, physics, chemistry and biology, all of the subjects that felt close to my heart. So, in spring 2008 I concentrated in studying for the entrance examinations and applied in to the Medical Faculty of the University of Helsinki.  

My medical studies started in autumn 2008 and I started my research at the same time. This work was later to become my thesis work. I met Professor Aila Rissanen from the Obesity Research Unit of University of Helsinki in the summer 2008 before my studies commenced and she enrolled me in her research group. Associate Professor Kirsi Pietiläinen became my supervisor. I applied and was accepted into the competitive MD/PhD programme in the Faculty of Medicine (Doctoral Programme in Biomedicine), which enabled me to do my medical studies and my PhD in medicine simultaneously.  

During the three to four first years, we extensively collected samples from our study cohort of young identical obesity-discordant twins. In 2013, I finally started writing the first article of my own. After graduating as an MD in the spring of 2014, I continued my thesis with full-time research work in our unit, the Obesity Research Unit and FinMIT – Center of Excellence in Research on Mitochondria. At that time I was also awarded the Best Licentiate Thesis Award of the Year 2013 by the Faculty of Medicine for my work. Gradually, my first articles were being published from 2014 on and some also received media attention, like the study on metabolically healthy and unhealthy twins with obesity in Diabetologia in 2014, and another study on mitochondrial biogenesis, which was published in Diabetes in 2015 alongside a companioneditorial on the subject.  

We would love to learn more about your country and the area in Finland you live in. 

Finland is a wonderful country to live in. We have such a lot of nature and wilderness, but we are still a very modern country with educated people and safe and peaceful surroundings. The standard of scientific and medical research is very high. We are often in the front line in terms of technology and innovation, which enables progress and makes doing research here very interesting. Finnish people can often appear quiet and reserved at first glance, but are friendly, helpful and trustworthy when you get to know them better. They keep their word and are also hardworking and perseverant. Finnish nature is beautiful especially in the summer with long light nights. We have a lot of forests, lakes and wild animals. In winter, Lapland is a great place to see, and snow makes everything so bright. However, it may also be very cold during the winter months and during the time before the snow falls in November and December it is definitely very dark, rainy and windy. The amount of light in the southern Finland can be only 6 hours and in the north there is no daylight at all. I live in the Helsinki area, which is the capital city of the country and the surroundings which arehome to over 1 000 000 people. By European standards however, that might be considered a small town. Finland indeed is a sparsely inhabited country with only around 5.5 million people and 15 people/square kilometer. 

How did you come to enter the field of obesity?  

Already before my medical studies I was interested in medical research and the MD/PhD programme based within the Faculty of Medicine in the University of Helsinki. However, my entryinto the field of obesity, adipose tissue and mitochondria was very much a coincidence. Before starting my medical studies, I met Professor Aila Rissanen of our Obesity Research Unit onan unrelated occasion in the summer 2008, which resulted inher telling me that she wanted me to work in her unit. I started working with my supervisor MD and Associate Professor Kirsi Pietiläinen by helping to take adipose and muscle tissue samples from our twin subjects, handling the samples, learning to extract pure adipocytes and their RNA and DNA from tissue, visiting our collaboration laboratories, Professor Peter Arner’s Lipid laboratory in Karolinska Institutet in Stockholm as well as Gema Fruhbeck’s Metabolic Laboratory in Pamplona, Spain, to acquire more biomedical techniques and then gradually acquiring data of my own and writing my first article. Both Kirsi and Aila trusted me with big and important projects, like extracting the RNA and DNA of our valuable twin material. All my research work I did in addition to my full-time medical studies – during weekends, holidays and summers.  

Gradually, as my studies and the other studies from our group on adipose tissue and adipocytes progressed, we started concentrating more and more on the mitochondria in adipose tissue. This was because all the gene expression results between the twins suggested that mitochondrial function and its various components were one of the most affected and changed gene-expression pathways between the obese and the lean identical co-twins that I was investigating. Particularlyintriguing was the fact that the changes in mitochondria-related gene expression, and in my later studies, differences in protein levels between the obese and the lean co-twins were seen at a very early stage in acquired obesity, in clinically healthy young twins, with a relatively short history of obesity. We also discovered that there were differences in the responses of obesity, possibly based on genetic differences between individuals, because some of the obese twins had more pronounced metabolic problems, more liver fat and larger adipocytes than other, similarly obese twins. And interestingly, there was also a difference in mitochondrial gene expression between these two groups.

In basic scientific research I am interested and intrigued by the possibility of producing something that in due course could help patients through understanding the basic principles of a disease and through the development of new medicines and new treatment strategies. I also like the basic research work in itself, because it is very variable and includes both clinical and laboratory aspects, writing, acquiring new information and learning new things every day. 

Congratulations on winning the highly competitive 2016 EASO New Investigators Basic Science prize. Please help us learn more about your thesis and present research interests:

In my thesis work, which is to be published this week, I have investigated the biological pathways in adipose tissue that lead to the development of metabolic complications in early-onset obesity in young healthy twins. The aim of the work was to study how acquired obesity affects adipose tissue and adipocyte function and how this links to whole body metabolism. Of special interest were the mitochondria and their function in obese adipose tissue. The rare weight-discordant monozygotic (MZ) co-twin setting used in the studies is uniquely positioned to disentangle acquired and inherited metabolic pathways to disease in obesity. Identical MZ twin pairs discordant for obesity enable controlling for genetic background, age, sex and early environmental influences. As MZ twins are fully identical at the level of genome sequence, the observed differences between co-twins can be assumed to be acquired. This is a major strength in a study regarding a polygenic and multifactorial trait as obesity.

Adipocyte hypertrophy in adipose tissue is one of the main features of obesity. The first study of my thesis investigated adipose tissue hypertrophy and hyperplasia in acquired obesity and its associations to whole body metabolism and gene expression pathways of adipose tissue. We showed a high within-pair resemblance in adipocyte size and number in twins suggesting that the adipocyte phenotype is genetic or due to shared environmental factors. Hypertrophy and low number of adipocytes in acquired obesity was related to metabolic dysfunction in obesity and associated with the disturbances in mitochondrial function and with increased cell death within the adipose tissue.

In the second study we investigated how transcriptional pathways of subcutaneous adipose tissue and the liver fat associate with “metabolically healthy obesity” – a phenomenon where some of the obese individuals stay free from the metabolic complications usually associated with weight gain. We showed for the first time in twins that the amount of liver fat is a key clinical determinant of metabolic health and that low liver fat associates with maintenance of high mitochondrial transcription and lack of inflammation in subcutaneous adipose tissue.

In the third and fourth studies of the thesis I addressed mitochondrial biogenesis and oxidative metabolism in detail in adipose tissue and in adipocytes, respectively. Obesity was related to reduced mitochondrial mass and oxidative metabolic activity in subcutaneous adipose tissue, both in the nuclear and in the mitochondrial transcription level, as well as decreased protein levels in the mitochondrial respiratory OXPHOS system, especially OXPHOS complex subunits I and IV. The mitochondrial ‘dysfunction’ paralleled whole body insulin resistance and low-grade systemic inflammation. Remarkably, these changes were seen already at the early stages of acquired obesity, in young otherwise clinically healthy twins. In the fourth study, we showed that the global downregulation of mitochondrial transcriptional signature in acquired obesity originates at least partly from the adipocyte cells of the adipose tissue.

According to my work, the development of obesity seems to associate with mitochondrial dysfunction in adipose tissue. The decreased function of mitochondria was evident at the level of both nuclear gene expression and mitochondrial gene expression, as well as on mitochondrial protein levels. These changes associated with metabolic disturbances of obesity. With rare obesity-discordant MZ twins we have been able to show that these changes are not genetic but result from acquired factors. However, as there was a remarkable similarity of adipocyte number between the co-twins, responses to obesity may have a partial genetic basis. With low capacity to adipocyte hypertrophy, excess fat may accumulate to liver and other tissues. Liver fat content seems to be a clear determinant of metabolic health in acquired obesity. The results of my thesis as a whole suggest that obesity-associated metabolic disturbances might be halted by improving mitochondrial activity in adipose tissue. 

In future, I hope to further pursue research on adipose tissue, adipocytes and their mitochondria. It would, for example, be very interesting to discover which kind of nutritional cues affect the obese and the lean adipocyte cells and thus what kind of nutritional and environmental surroundings would best help to reverse the metabolic problems of obese adipocytes. 

What are your future career plans?

My dissertation will be held this month – November 2016 – and thereafter I will graduate as a PhD in Medicine. I then still have some months’ funding as a full-time researcher, which enables me to start some new projects at my current lab before February 2017, when I’ll begin to work in basic health care as a general practitioner for 10 months. This is to keep up with my medical knowledge and to acquire the European medical standards as a doctor, thus to enable me to work as an MD in all other European countries in addition to Finland. I have also enrolled in the internal medicine specialization program in the University of Helsinki and will start with the internal medicine specialization after the general practicum. I then also wish to continue with my research and later on also combine it with my clinical work. I am interested in a Post Doctoral phase in research, either in Finland or in a country abroad, and the subject could be related to my own work or to another research area. By now, I have acquired a strong set of skills in clinical research as well as in various laboratory techniques and data analyses, and it will be interesting to use and develop them further with new research ideas. I hope to acquire funding to pursue some of the interesting research plans that we have been planning in our unit on identical obesity -discordant twins and also for a Post Doc in Finland or abroad.

Aside from your professional interests, what are your hobbies and interests?

During my free time I actively teach and lead my own contemporary dance group and work as an artistic director of astudents’ dance association. I also swim a lot. Swimming in the mornings gives me a lot of energy for my work. My other interests include baking and cooking, indoor-climbing, running, travelling and non-fiction books on life sciences and medicine. I love meeting with friends and just relaxing. 

Sini Heinonen, MD, PhD elect (25 November 2016)

Sini Heinonen is an MD and a PhD Student in Obesity Research Unit, Diabetes and Obesity Research Programs Unit, University of Helsinki, Finland. 

Sini Heinonen’s work has focused on the effects of acquired obesity in obesity-discordant monozygotic twins. Her interests are the study of adipose tissue and its mitochondria. She has studied adipose tissue enlargement, mechanisms maintaining the “metabolically healthy obesity” – and the downregulation of mitochondrial biogenesis and its relation to metabolic health in obese adipose tissue and adipocytes. Sini Heinonen was awarded Young Investigator Award of the European Obesity Society in basic science in 2016. Her work has also been granted support from various Finnish medical and scientific associations, as well as the Award of The Best Licentiate Thesis of the year 2013 from the Faculty of Medicine in Helsinki. Sini Heinonen graduated as an MD in 2014 and will finish her PhD in November 2016.

Sini has worked in Obesity Research Unit and FinMIT -Center of Excellence in Research on Mitochondria since 2008. She has extended her knowledge with visits and collaboration in Metabolic Research Laboratory, Pamplona, Spain and Lipid Laboratorium, Karolinska Institutet, Sweden, as well as NUTRIM School of Nutrition and Metabolism, Human Biology, Maastricht University, The Netherlands. She has presented her data in various international and national conferences since 2010. Along with her research work Sini Heinonen is in the specialist training program of internal medicine at University of Helsinki.