The composition of adipose tissue: what is its impact on obesity?

Considered a major public health problem by the World Health Organisation (WHO), obesity affects around 19.5% of people in the OECD. Concerning mainly industrialised countries, obesity is growing in all parts of the world and in all social categories.

Global bodies such as the WHO and health authorities in many countries, such as France, have implemented policies for the prevention and treatment of obesity and its underlying pathologies. The treatment of obesity is mainly based on the reduction of body fat, which is singled out as a risk factor, proven or assumed, for the development of metabolic and cardiovascular disorders.

This is an assumption that the UMR1231-LNC (Lipids Nutrition Cancer) team wanted to reconsider with the partners of the FUI SYMPPA project, by demonstrating that the quality of adipose tissue, or body fat, has as much, if not more, influence than its quantity on the development of pathologies linked to being overweight, and that obese individuals do not all have the same risk of developing underlying pathologies, such as cardiovascular diseases, insulin resistance and type 2 diabetes.

Do all obese people really suffer from pathologies linked to their weight? How does the quality of adipose tissue, even more than its quantity, intervene in the development of metabolic and cardiovascular disorders?

Here are a few answers provided by Laurent Lagrost, research director at UMR1231-LNC (supervising the University of Burgundy, INSERM and AgroSup) and partner of the FUI SYMPPA project.

What is "Low metabolic risk obesity"?

Obesity: a public health concern

The WHO defines obesity as an abnormal or excessive accumulation of body fat that represents a risk to health. An individual's obesity is commonly measured by the Body Mass Index (BMI). This is the ratio between the height and weight squared of the individual. With a BMI equal to or greater than 25, the individual is considered to be overweight; from 30 he or she is considered obese.

A too rich diet, a lack of physical activity, genetic predisposition, behavioural disorders... The causes of obesity are manifold and vary from person to person. Considered a public health problem, obesity is a risk factor for other chronic diseases such as diabetes, cardiovascular diseases, or cancer.

The prevention messages deployed by health agencies warn of the serious consequences of obesity for health. Should we conclude that an obese person will necessarily suffer from an underlying pathology? It is this popular belief that Laurent Lagrost wishes to discuss: "Without questioning the dangers associated with obesity, scientific observations have shown that it is probably restrictive and too simplistic to want to predict the risks of metabolic and cardiovascular complications only according to the quantity of body fat."

The concept of obesity with low metabolic risk

Do all people with obesity suffer from related metabolic and cardiovascular disorders? This is the question that a Finnish research team wanted to answer by observing the state of health of 16 pairs of monozygotic twins with differing levels of obesity, that is to say, each composed of an obese individual and of a non-obese individual (source: medscape.com). The observations made it possible to observe that 50% of obese individuals were healthy and metabolically identical to their thin relative, that is to say that they did not present any of the pathologies classically linked to obesity. Large disparities were observed: among the cases in which the obese subject did not present metabolic disorders, his/her percentage of hepatic fat was significantly equivalent (+ 8%) to that of his/her thin twin, whereas in the group where the obese subject suffered from pathologies related to overweight, the percentage of liver fat was 718% higher than in the thin twin.

Other metabolic factors were analysed and each time the metabolically healthy obese twin had results equivalent to his/her thin twin and did not show an increase in cardiometabolic risk.

Since the characteristics (age, sex, tobacco and alcohol consumption, physical activity, and daily energy intake) of each pair of twins were similar, how can we explain these disparities regarding obesity? Differences in the composition of adipose tissue have been observed, but the mechanism linking adipose tissue to the risk of suffering from a metabolic pathology have not been proven.

SYMPPA project: the importance of the composition of adipose tissue

The FUI SYMPPA* project (Metabolic syndrome: Developing new active ingredients of natural origin aimed at restoring lipid/carbohydrate metabolism via active polyphenols) focused on the phenomenon of obesity with low metabolic risk. “Our objective was to demonstrate experimentally that the composition of adipose tissue and its quality influence the risks of developing metabolic disorders and underlying pathologies," explains Laurent Lagrost. The medical treatment of obesity is most often only considered by the means of the loss of body fat, without taking interest in its quality. "The whole originality of this study was to consider adipose tissue not only in terms of quantity, but also and especially in terms of its cellular and molecular composition," adds Laurent Lagrost.

* Composition of the consortium: UMR 1231 LNC (INSERM), Spiral Laboratory, Eurial Ultra Fresh, Salins du Midi. This project was supported and labelled by Vitagora. The program began in 2013 for a period of three years and the results were disclosed in 2019.

The project’s research program

To prove the hypothesis that the quality of adipose tissue plays a key role in the development of metabolic and cardiovascular pathologies associated with obesity, the team of researchers analysed the adipose tissue and the metabolism of three groups of mice:

• A control group of mice fed a balanced diet and having an average weight of 30 g.
• A group of mice made obese and fed a diet rich in fat and carbohydrates with an average weight of 60 g.
• A group of these same mice made obese with an average weight of 60 g, having received in addition a polyphenolic extract rich in various antioxidants, developed by the LaraSpiral Laboratory.

Several observations were made:

The metabolism of the obese mice which did not receive the polyphenolic extract as a supplement was considerably altered compared to that of the lean mice. Their life expectancy was reduced by 36%. The obese animals suffered in particular from hyperglycemia and hypercholesterolemia. By examining the composition of adipose tissue, the researchers found a significant infiltration by pro-inflammatory immune cells that can promote the development of pathologies.

Conversely, the life expectancy of obese mice which received the polyphenolic extract as a supplement was almost equivalent to that of the thin mice and their metabolism was much more balanced than the other obese mice. The researchers found in these mice a better lipid balance, a decrease in oxidative stress and a reduction in adipose tissue infiltration by immuno-inflammatory cells compared to the non-supplemented obese mice of equal body mass.

Encouraging results

The use of polyphenol extract allowed the team of researchers to correct adipose tissue anomalies generated by a fatty and sweet diet. The life expectancy of obese mice was improved enough to return to the same level as non-obese mice despite the greater amount of body fat. "Thus, for the first time, it has been shown experimentally that the composition of adipose tissue, rather than its quantity, contributes to the development of pathologies linked to obesity," notes Laurent Lagrost.

And in humans?

What public health repercussions could there be if these results are confirmed in humans?

As a first-line treatment, more attention should be given to the composition of adipose tissue when evaluating risk factors and complications related to obesity, and no longer focus solely on the amount of body fat and body weight of one person. Then, it could be considered that a balanced diet rich in antioxidants could modify the composition of adipose tissue by limiting the phenomena of oxidation and infiltration of immuno-inflammatory cells. “The next step will be to search subjects suffering from obesity for evidence supporting these hypotheses,” underlines Laurent Lagrost.

Beyond the results of this study, Laurent Lagrost invites us to consider adipose tissue as an organ in its own right. “A better understanding of the composition of adipose tissue, its mechanisms and its influence on metabolism would shed new light on the prevention and care of obesity, in particular through individualised medical treatment and the development of a personalised nutritional approach,” he concludes.

Keywords

Obesity, adipose tissue, prevention, metabolic disorders, health

Further reading

Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract, Virginie Aires, Jérôme Labbé, Valérie Deckert, Jean-Paul Pais de Barros, Romain Boidot, Marc Haumont, Guillaume Maquart, Naig Le Guern, David Masson, Emmanuelle Prost-Camus, Michel Prost and Laurent Lagrost. Scientific report, 2019