Obesity is defined by excessive body fat which causes health problems and reduces life expectancy. Its causes are complex: in addition to nutrition and genetics, numerous environmental factors appear to be implicated in the development and persistence of this chronic disease. Acquiring a better understanding of the causes and biological mechanisms resulting in obesity is now one of the greatest challenges facing research. Like all chronic disorders, obesity becomes irreversible once it takes hold: preventing it from developing is therefore crucial if we are to curb this global epidemic.

  • Throughout the world, 35% of adults are obese or overweight
  • Throughout the world, 2.8 million deaths per year
  • Adipose tissue of people with obesity present abnormalities
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Report drawn up in collaboration with Arnaud Basdevant, nutritionist and scientist, Inserm Unit 872, ICAN university hospital institute (Institute of Cardiology Metabolism and Nutrition, Paris), Chairman of the National Plan on Obesity 2010-2013

Loupe comprendre Understanding obesity

A disorder which adapts to recent lifestyle changes, obesity is the result of an imbalance between the number of calories consumed and calories burned. This imbalance vastly increases the reserves stored in fatty tissue, which then causes numerous complications.

Obesity currently affects practically the whole planet, including emerging countries: according to the World Health Organization (WHO), 35% of adults worldwide are obese or overweight. The associated complications, particularly diabetes and cardiovascular disease, result in the death of at least 2.8 million people each year. In France, 15% of adults were obese in 2012, as opposed to only 6.1% in 1980. However, more recent data, from 2012, are more hopeful: for the first time in over 30 years, the progression of obesity is finally starting to slow in this country.

Obesity, a disorder with many consequences

Obesity gives rise to health problems, the main ones being type 2 diabetes (the disease is associated with obesity in 80% of cases), hypertension, elevated blood lipid levels (dyslipidemia), cardiovascular disorders, sleep apnea syndrome and other respiratory disorders, together with joint disease, such as osteoarthritis. Obesity is, moreover, associated with an increased risk of certain types of cancer, particularly endometrial cancer (cancer of the uterus). The psychological and social impact of this disorder, which causes many patients to seek medical advice, should also be highlighted.

[In French] Obesity and complications - interview - 4 min 09 - video from the POM Bio à Croquer series (2013)

Pictogramme personne surpoids Determination of excessive body fat

Obesity is often diagnosed using the body mass index (BMI), which is currently the only straightforward method for estimating a person’s body fat. BMI is a person’s weight (in kg) divided by height squared (in meters). According to the WHO classification, a person is overweight when the BMI is over 25, and obese when this exceeds 30. For children, the growth charts depicted in the child health records serve as guidance.

BMI in kg/m2

WHO classification

Under 16.5

Severely underweight

16.5 to 18.5

Underweight

18.5 to 25

Reference values

25 to 30

Overweight

30 to 35

Moderately obese

35 to 40

Severely obese

Over 40

Very severely obese

Gouttelettes lipidiques de cellules adipocytaires.
Adipocyte lipid droplets © Inserm, Lacasa, Danièle

However, caution should be exercised when interpreting this table: body make-up can, in fact, vary from one individual to another, for a given BMI. Hence, a pregnant woman or high-level athlete will have a high BMI despite not have excessive body fat.

Another criterion is also taken into account when estimating whether a patient is obese: waist measurement. Excessive body fat around the waist is associated with an increased risk of diabetes and cardiovascular disease, regardless of the BMI. When the waist measurement is greater than 100 cm in males, and 88 cm in (non-pregnant!) females, this is defined as abdominal obesity.

Pictogramme morceaux de sucre Multiple causes

Obesity has numerous causes, and identification of the factors implicated in its development and persistence is far from complete.

[In French] The vicious cycle– an educational animated short film – 3 min 15 – video from the series On board the Nanotilus (2012)

Dietary changes and decreased physical activity play an unquestionable role in the recent emergence of obesity. Larger portion size, higher calorie density, food availability, and changes in food prices are some of the factors which promote excessive calorie intake. Pastimes such as watching television or playing video games, taking the car or using public transport for everyday travel also result in lower energy expenditure.

However, these factors which influence the caloric balance, hence nutritional status, are not enough to explain the growing incidence of obesity, or the differences among individuals in terms of weight gain: some people gain weight more easily than other, despite having the same lifestyles.

A genetic predisposition to gaining weight may account for these differences in individual susceptibility to obesity. Several French teams from Inserm and CNRS have identified numerous genes implicated in weight gain, severe obesity and/or the complications of obesity.

The environment also appears to play a major role. Stress, sleep, certain medications, viruses, the composition of the intestinal flora, and exposure to pollutants are likely to be other potential factors. Early exposure and events evidently play a key role, including those occurring before birth or, indeed, gestation. The influence of maternal diet on the development of obesity has been examined in particular in the Elfe study.

Pictogramme chirurgien Which approach to management?

Recent advances in the management of obesity stem from a more general approach, taking into account both behavioral and environmental dimensions. Preventing and treating complications is the focus of this management approach.

While medicinal treatments specific to this disorders are very limited, surgery for obesity is greatly expanding. This is reserved for the most severe forms associated with complications. Numerous clinical research programs are studying this type of surgery, the efficacy (and side effects) of which may provide important information on the mechanisms involved in the development of the disorder and its resistance to conventional therapies.

Comprehensive, tailored management of obese patients is essential when faced with such a heterogeneous clinical entity: the data collected show that the impact of vastly increased body fat on health depends not only on the extent but also the nature of this excess fat (degree of inflammation, cell size), its distribution (abdominal, around the liver, heart, etc.) and the resulting complications.

There is no standard treatment or "miracle solution", but a need to adapt the therapeutic strategy to the individual situation.

Specially tailored treatment centers

The Plan on Obesity 2010-2013 led to the creation of specialist centers and multidisciplinary integrated centers. These specialist centers, 37 in total, are spread throughout the various regions of France. These have multidisciplinary medical teams and equipment adapted to the management of severely obese patients. The five integrated centers, moreover, have the capacity to carry out highly specialized diagnostic and treatment procedures (i.e., genetic, rare diseases), and are actively committed to research (through partnerships with Inserm research units), training, teaching, and innovation.

Pictogramme microscope Challenges facing research

Acquiring a better understanding of the causes and biological mechanisms resulting in obesity is now one of the greatest challenges facing research. Like all chronic disorders, obesity becomes irreversible once it takes hold: preventing it from developing is therefore crucial if we are to curb this global epidemic.

Pictogramme personne surpoids At the heart of obesity

Obesity is a disorder of adipose tissue ("fat"). This tissue contains cells which store energy reserves in the form of fat: adipocytes. These cells become hypertrophied (increase in volume) as they accumulate lipids. When they reach their maximum volume, they are able to recruit new "empty" cells ready to load fat. Hence, adipose tissue mass expands not only due to the increase in adipocyte volume, but also due to the increased number of its constituent adipocytes. Current research aims to study the capacity of adipose tissue to recruit new adipocytes under the influence of certain nutrients, infectious agents, pollutants, nerve or hormonal factors.

Adipocytes en culture obtenus à partir de cellules souches mésenchymateuses (gouttelettes lipidiques en jaune, noyaux en bleu).
Adipocytes in culture obtained from mesenchymal stem cells (lipid droplets in yellow, nucleic in blue). © Inserm, F. Blanchard

Furthermore, it was recently discovered that adipocytes only constitute a third of cells making up adipose tissue. The remaining two-thirds consist of stem cells, lymphocytes and other immune system cells, vascular cells, and nerve endings, etc. The role of adipose tissue is not therefore limited to fat storage: it receives information, essentially from the brain and gastrointestinal tract; it is also capable of producing numerous substances, adipokines, signals which it sends to the central nervous system, liver, muscles, heart, blood vessels and intestine, etc. In obese individuals, this dialog between adipose tissue and the rest of the body is impaired, with two-fold consequences: a steady increase in weight which is increasingly difficult to control, and the onset of hepatic, cardiac, respiratory, joint complications, etc.

A major abnormality characterizing adipose tissue in obese individuals is inflammation related to immune system cells, macrophages, infiltrating into the adipose tissue. This phenomenon lies at the center of the mechanisms generating the long succession of obesity-related complications. This is associated with abnormal production of adipokines which contribute to complications affecting other organs. Furthermore, inflammation leads to tissue fibrosis which is a factor for resistance to weight loss. The mechanisms triggering the infiltration of pro-inflammatory cells into the adipose tissue, and the resulting disruption, have yet to be determined.

Another major field in obesity research aims to identify the mechanisms which cause the central nervous system, the hypothalamus in particular, to become incapable of curbing food intake and increasing energy expenditure when faced with excessive body fat. The neuroscience field is leading this approach.

Furthermore, the scientists are focusing on the role of the intestine, hormones secreted by the gastrointestinal tract, and the intestinal flora in the mechanisms leading to weight gain. Regarding the latter aspect, recent research has shown that the quality of the intestinal flora may be associated with greater or lesser susceptibility of developing metabolic disorders related to obesity.

[In French] State of research: Microbiota and obesity - interview - 3 min 19 - video from the Corpus platform (2014)  

Lastly, as obesity is a source of social health inequality, the field of human and social science is being enlisted in order to shed light on the societal determining factors at stake (economic, behavioral, social) for this disorder observed in the context of economic transition, which particularly affects individuals in precarious situations.