Weight gain and "-omics"
Researchers at Stanford University claim that even during short periods of increasing and decreasing body weight, the human body undergoes serious changes affecting the composition of the microbiome, the cardiovascular system, as well as gene expression levels.
The authors integrated a variety of technologies known as "-omics" to collect a huge amount of data revealing unique details about the genomic, molecular, metabolic and bacterial composition of the organisms of the study participants. The ending "-omika" is equivalent to attaching the word "study" to the name of the field of biological research. For example, "genomics" is the study of genes, and "proteomics" is the study of proteins.
According to one of the leaders of the study, Professor Michael Snyder, the aim of the work was to obtain an unprecedented detailed description of the processes occurring in the body during the increase and decrease in body weight. In addition, they wanted to find out how individual "-ohm" profiles and reactions to fluctuations in body weight of people predisposed to the development of diabetes mellitus differ.
The results demonstrated that even a moderate increase in body weight (by about 3 kg) causes very strong changes in the body at the molecular level. Bacterial populations are transformed, immune responses and inflammatory processes are intensified, and molecular mechanisms associated with the development of diseases of the cardiovascular system are activated. However, this is not the end of the story. When the body weight of the study participants decreased again, the state of most systems of their organisms returned to their original state.
The mechanisms triggered by changes in body weight at the microlevel in the body of people with insulin resistance, which is a manifestation of impaired glucose processing ability and a common precursor of type 2 diabetes, were of the greatest interest to researchers. To do this, they compared the differences in the basic results of the examination of insulin-resistant and healthy participants obtained with the help of "-omic". After that, the authors analyzed 2 main questions: How does weight gain affect the "-ohm" profiles? And what happens after weight loss?
Billions of dimensions
A total of 23 people took part in the study. 13 of them had manifestations of insulin resistance, and 10 had a normal ability to assimilate glucose. All of them had body mass index values ranging from 25 to 35 kilograms per square meter of body surface area. (25 is the upper value of the normal range, whereas 40 roughly corresponds to malignant obesity.) For each of the participants, the authors gathered together information about a transcriptome – a complex of molecules reflecting DNA expression profiles, a proteome – a complete complex of proteins produced by the human body, a microbiome and a genome. According to Snyder, in the end, the researchers had literally billions of measurements at their disposal.
Even at the beginning of the study, the authors found significant differences between the baseline parameters for insulin-resistant and non-insulin-resistant participants. Among the discrepancies in the parameters of protein production and the population composition of the microbiome, they identified one particularly striking feature: molecular markers of inflammation were detected only in the bloodstream of insulin-resistant participants. Inflammation is a problem characteristic of patients with diabetes mellitus and conducting an early "-om" examination will help in identifying inflammation-associated molecules in people who do not have diabetes, but are at risk.
After studying the differences at the basic level, the authors began to change the parameters. Participants began to receive a high-calorie diet and in 30 days their body weight increased by an average of 3 kg. The change in body weight, despite moderation, was accompanied by a shift in the "-ohm" profiles. Levels of inflammatory markers increased in participants of both groups. The insulin-sensitive participants experienced an increase in the population of the bacteria Akkermansia muciniphila, known for its ability to prevent the development of insulin resistance. However, the most impressive change was a shift in the level of expression of genes associated with an increased risk of developing a certain type of heart failure – dilated cardiomyopathy, in which the heart loses the ability to effectively pump blood through the body.
Reducing the participants' body weight to baseline values ensured the restoration of almost all the assessed indicators, including the population composition of the microbiome, as well as the levels of various molecules and gene expression. However, a small number of changes in the production of protein and other compounds persisted, which indicated the possible long-term nature of a number of effects. At the same time, the authors note that to date they do not have enough data at their disposal to make unambiguous clinical conclusions.
Another important detail is the fact that, despite the existence of certain trends in the shifts of the "-ohm" profiles, each participant demonstrated individual changes in various parameters. This highlights the critical importance of deep integrative analysis of a wide range of data in the diagnosis and treatment of patients.
Article by Brian D. Piening et al. Integrative Personal Omics Profiles during Periods of Weight Gain and Loss is published in the journal Cell Systems.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Stanford University School of Medicine: Weight flux alters molecular profile.