Early detection of changes resulting from obesity is a very difficult area of diagnosis. Currently used markers and measures, such as body mass index (BMI), often do not allow for a realistic assessment of the patient's condition because they do not continuously track pathology at the systemic, tissue and cellular level.

The team led by Dr. Magdalena Szczerbowska-Boruchowska from the Department of Medical Physics and Biophysics, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology in Kraków, and Dr. Agata Ziomber-Lisiak from the Department of Pathophysiology of the Jagiellonian University Medical College decided to search for new, more reliable diagnostic markers. The method tested by the researchers was the analysis of the concentrations of chemical elements in the body's tissues, in particular trace elements. They described the results of their work in the journals Biochimica et Biophysica Acta and International Journal of Molecular Sciences.

'Trace elements have a number of important roles in processes related to the proper functioning of the body,’ Dr. Magdalena Szczerbowska-Boruchowska tells PAP. 'They take part in numerous tissue processes: they are building materials, they participate in enzymatic reactions, energy metabolism and conduction of electrical impulses. Although, due to its complexity, the biochemical mechanism of obesity development is not fully understood, it is known that as a pathological process it impairs the proper functioning of tissues, which involves trace elements. Previous studies have already indicated certain anomalies regarding their levels in the blood serum and hair of obese people.'

Dr. Ziomber-Lisiak adds that doctors currently have several markers, on the basis of which they try to diagnose the early stages of obesity. These include: high triglycerides and low HDL, hypertension and increased plasma glucose levels. However, all of them, just like the popular BMI, are very unreliable. There is a group of obese people who are 'metabolically healthy', i.e. the above indicators are within the normal range. And contrary to appearances, as the authors of the publications emphasize, this is not a completely favourable situation. Although these patients are less likely often than typical obese people to suffer from metabolic disorders, insulin resistance and type 2 diabetes with classic complications of their disease, this group is characterized by a higher mortality rate than the general population, mainly due to cardiovascular complications.

'The causes of this phenomenon have not yet been precisely explained, which suggests that we have not yet learned about all possible disorders and consequences of excessive body fat and that these standard markers cannot detect all pathologies associated with excess adipose tissue,’ says Dr. Ziomber-Lisiak.

Therefore, both scientists and their colleagues decided to use analytical tools based on X-ray fluorescence analysis to monitor changes in trace elements in rat tissues that occur with the development of obesity. Their goal was to identify markers of the early stage of obesity among less standard 'candidates', i.e. chemical elements.

Early and late obesity

'We introduced the division into early and late obesity based on the time of administering a high-calorie diet (HCD) to the study animals; this limit is not clearly defined in the literature,’ says Ziomber-Lisiak.

'In our experiment, the duration of administration of this diet was relatively short - 7.5 weeks. After this time, we found a statistically significant difference in the increase in body weight, especially fat tissue, compared to the control group, which allowed us to diagnose obesity.’

The expert emphasises that it is difficult to compare the stages of obesity in rats and humans due to factors such as different average lifespans, but it can be assumed that the shorter the duration of HCD diet administration, the earlier the stage of the disease.

The researchers used both analytical methods to determine the elemental composition of tissues, and innovative data mining methods. To determine the elemental composition of tissues, total X-ray reflection fluorescence analysis (TXRF) was used, allowing to detect many elements, even in very low concentrations (µg/kg).

Based on this, scientists determined element content differences in tissues between obese and non-obese animals and indicated which parameters contributed to the distinction between these two groups. Ultimately, they identified potassium, iron, bromine and rubidium as potential chemical markers of obesity. The next stage of research clearly showed that the strongest differences between healthy and sick individuals occur in the case of rubidium.

Element content differences in a healthy and obese body

The researchers explain that first it was necessary to eliminate the potential impact of diet, and not obesity itself, in the differences in the elemental composition of tissues of sick and healthy animals. To that end, the researchers analysed their food and determined how much of each element animals absorbed with food. The results did not confirm the relationship between the amount of the element taken up with food and its concentration in tissues (potassium was the only exception).

'We therefore concluded that the observed changes in the levels of elements in obesity were a manifestation of more complex metabolic processes, nbot just a simple reflection of the amount of the consumed element,’ says Dr. Szczerbowska-Boruchowska.

As for rubidium itself, its concentration was significantly higher in the group of obese individuals compared to those not suffering from obesity. This proves that this element has the greatest diagnostic power among all those tested. 'It turned out to be the best predictor in classifying individuals in terms of obesity,’ she says. ‘It was the only one to show higher concentrations in all organs of obese individuals, and its level strongly correlated with the previously mentioned well-known metabolic markers of obesity.’

BMI is not a perfect indicator

Dr. Ziomber-Lisiak also explains why the BMI index, commonly used in dietetics and medicine, is not the optimal method for assessing the amount of fat tissue in a given person.

'This method has its limitations, for example, it is not used in children (due to different body proportions) and sometimes it may distort the patient's body composition, e.g. in a strongly built person with a lot of muscle tissue, because muscles weigh a lot. Moreover, BMI does not tell us anything about the distribution of fat in the body, and we know that the most dangerous location for health is the visceral location, i.e. abdominal obesity.’

A much better method of assessing the amount of visceral fat tissue would be analysis with imaging tests, such as computed tomography, magnetic resonance imaging or DEXA, but due to time and costs, these procedures are not commonly used. That is why it is so important to find new methods of identifying people whose body fat is particularly dangerous.

More effective protection against the complications of obesity

The Krakow researchers summarise that the main goal of their study was to expand knowledge about the pathogenesis of obesity and its complications, which may contribute to their faster and easier detection. 

'Treatment of this disease is long, expensive and often ineffective, which is why we are searching for early markers to help clinicians prevent advanced and irreversible disorders secondary to excessive body fatness. This particularly concerns the group of obese but +metabolically healthy+ patients who do not suffer from typical disorders, so they have no motivation to change their lifestyle, the scientists say.

PAP - Science in Poland, Katarzyna Czechowicz

kap/ agt/ kap/

tr. RL