Obesity is currently recognized as an epidemic and one of the most
important health problems worldwide. World Health Organization data indicates that in
developing countries, obesity in adults is more frequent than malnutrition. More than
1.9 billion adults are overweight, with 650 million of these being obese. More than 200
million school-aged children are overweight, making this generation more likely to
have a shorter productive life and life expectancy than their parents. This portion of the
population has a greatly increased risk of developing cardiovascular disease, diabetes,
dyslipidemia, hypertension, hepatic steatosis, certain types of tumor and infertility,
negatively impacting their quality of life. Obesity can be prevented and is treatable
with the adoption of a healthy and appropriate diet, and with regular physical exercise.
However,lifestyle modification therapy for the obese population remains
unsatisfactory. In addition, it is important to emphasize that obesity treatment presents
better results when accompanied by a multidisciplinary team, using diet therapy,
prescribed physical exercise, psychotherapy and drug therapy, according to the needs
of each patient. Obesity is a multifactorial, complex, chronic and relapsing disease
involving gene-environment interaction and should therefore be treated with a systemic
and ecological approach. This is because many roles of intestinal microbiota in human
health have recently been discovered, mainly in relation to weight gain or loss.
Additionally, recent studies suggest that human gut microbiota may contribute to the
regulation of multiple neurochemical and neurometabolic pathways through complex systems that interact and interconnect the gastrointestinal tract, skin, liver, and other
organs, such as the central nervous system. The brain and intestine form a complex
nervous, endocrine and immune bidirectional communication axis, involving
neurotransmitters and neuromodulators. Changes in one organ will affect other organs,
and disturbances in the composition and number of intestinal microorganisms can
affect the enteric and central nervous systems. Alterations in intestinal microbiota may
increase intestinal barrier permeability, raising the risk of developing chronic diseases,
like obesity. Furthermore, the imbalance between gut microbiota and its host leads to
dysbiosis, which, in turn, contributes to the establishment of an inflammatory and
oxidative process, impaired glucose metabolism, insulin resistance, obesity, increased
risk of developing of metabolic syndrome, type 2 diabetes, inflammatory bowel,
autoimmune diseases, and cancers. Studies have shown that less-industrialized
populations, such as those in Africa, present a more diversified gut microbiota that is
richer in terms of bacterial genera, which encode enzymes that hydrolyze cellulose and
xylan. This finding suggests these individuals have a fiber-rich diet, a different
situation from industrialized populations who obtain energy from an ultra-processed
diet, rich in fats, salt, sugars and preservatives, and who present a high prevalence of
obesity and other chronic diseases. In this sense, it is fundamental to reflect on what
type of anti-obesity drug should be developed to treat this pathology, as most of these
drugs act on the central nervous system and, therefore, interfere in communication
between the brain and intestine. It is important to develop an anti-obesity drug that acts
not only on appetite control and on increased satiety, but also engages with and is
friendly to intestinal microbiota, via increased diversity of this ecosystem, decreased fat
storage and chronic oxidation inflammation, and correct modulation of the immune
system. Nonetheless, we must not forget that obesity is a complex and multifactorial
disease, and that its drug treatment must be combined with a healthy and adequate diet,
physical exercise and cognitive-behavioral therapy. Within this context, this chapter
aims to promote reflection around this theme and to provide the theoretical foundation
for development of the next generation of anti-obesogenic drugs.
Keywords: Anti-Obesity Agents, Appetite Depressants, Diet, Drug Effects, Drug
Interactions, Drug Therapy, Gastrointestinal Microbiome, Microbiota, Metabolic
Side Effects of Drugs and Substances, Obesity, Physiological Effects of Drugs,
Reducing.
