Changing lifestyle has turned out to be a very difficult way to escape obesity. The human body has extremely strong mechanisms for retaining fat. This explains why researchers increasingly believe that the obesity epidemic will be conquered by learning to understand the mechanisms in our brain and fat tissue. Researchers mapped which genes are expressed in fat tissue – 13 years before they knew whether the participants gained or lost weight. The results show a clear profile and also indicate potential ways of helping the body lose weight.
A few years ago, most people thought that hunger was a feeling that was simply controlled by the brain and that overweight could therefore be combated merely by influencing brain signals. However, research in recent decades has shown that this process involves interaction between hundreds of genes expressed in the brain and in fatty tissue. To determine how this interaction affects our metabolism and weight, researchers analysed fat tissue samples from more than 50 women and then examined whether the women lost or gained weight in the following 13 years.
“The women who lost weight especially had changes in the insulin response, fatty acid turnover and where the inflamed fatty tissue was. The women who gained weight had a change in the processes breaking down the components of the cells: autophagy. Based on the profile in the fatty tissue, we can thus predict whether women will lose or gain weight. We hope that this knowledge will help us to understand the processes in fatty tissue better so we can find new ways to help overweight people lose these dangerous extra kilos,” explains Ingrid Dahlman, Adjunct Professor of Diabetes Research, Department of Medicine, Huddinge, Karolinska Institutet, Sweden.
Protecting against inflammation
The new experiments provide a unique perspective over time, since previous attempts to characterize metabolic differences among overweight people have usually merely provided a snapshot of people who have become overweight. These experiments followed a group of women over many years. In addition, instead of examining changes in the DNA code of the genes, the researchers investigated which genes were actually expressed in the fatty tissue.
Since the expression of individual genes differs greatly in different tissues at different times, we decided to measure which genes are translated from DNA to RNA because this tells us which genes actually become active in the tissue. If the gene expression is higher among overweight people than among people with normal weight, these genes have probably significantly influenced whether these people gain weight.
The profile of the gene expression among the women who had lost weight during the 13 years did not surprise the researchers. High expression of genes that promote the insulin response and high fatty acid turnover indicate active and healthy fatty tissue. Further, recent research has shown that inflamed fatty tissue is unhealthy tissue. The lower expression of genes that promote inflammatory factors was also not surprising. The profile of the overweight women was a little more surprising.
“The women who gained weight during the 13 years had increased autophagy: the processes in the cell that degrade and recycle damaged proteins and organelles. This may protect against the increased inflammation of the fatty tissue among overweight people, but we are not certain why the activity is higher.”
Although the study is not the first of its kind, no thorough studies of fatty tissue had been done over this many years. Unfortunately, the study did not have enough men participating to conclude whether the same conditions apply to men. The study focused on the participants’ white fat, since this is the type of fat most associated with health problems.
“The results for the increased activity of the autophagy-promoting genes open up a whole new field of research. By understanding why these genes are regulated differently among overweight people, we may be able to determine what is happening in the white fat and why some people accumulate more white fat and then have difficulty in shedding it again. If we learn to understand the mechanisms, we can potentially find ways of normalizing the fatty tissue again.”
The researchers have some clues and theories as to the direction they should take. Among the women who lost weight, the expression of the COL6A1 gene was noticeably higher. This gene promotes a component of type IV collagen, a major part of connective tissue.
It is therefore possible that low expression of this gene can weaken the connective tissue, thereby enabling the fatty tissue to expand more than normal. This is just one of many factors, but it demonstrates the potential of the studies and offers hope that we can learn even more about why unhealthy white fatty tissue expands and how, over time, we might learn to reduce this with medicine.
“Prospective analyses of white adipose tissue gene expression in relation to long-term body weight changes” has been published in the International Journal of Obesity. In 2018, the Novo Nordisk Foundation awarded a grant to Ingrid Dahlman for the project The Role of Adipose Tissue in Cardiovascular Disease with or without Diabetes.