Pathophysiology of Obesity

Fig. 2.1

The hypothesis of a role of the gut in the pathophysiology of obesity and diabetes. A dysfunctional intestinal signal is posited to be involved in the pathophysiology of obesity and T2DM. According to this hypothesis, overstimulation of the gastrointestinal tract (by overeating and/or the presence of chemical or biological stimuli in modern diets) could lead to insulin resistance, obesity, and T2DM, whereas all forms of restriction of nutrients’ transit could improve these conditions. Indeed, diet might improve obesity and diabetes not just because of a restriction of caloric intake but also possibly because of the reduced stimulation of abnormal intestinal mechanisms. Likewise, restrictive surgery could improve obesity and T2DM by reducing the nutrient load even further. Bypass operations, which completely and indefinitely inactivate a large part of the intestine, reduce nutrient-related stimuli more than any other approach and are the most effective ways of improving T2DM, obesity, and insulin resistance syndrome (GI gastrointestinal; T2DM type 2 diabetes mellitus)

The epidemic growth of the incidence of obesity and T2DM suggests that environmental or infectious agents could contribute to the development of these diseases. Although considering the rising incidences of obesity and T2DM from the perspective of an infectious epidemic is highly speculative, this is supported by some recent studies [63] for several reasons.

Since the gastrointestinal tract is involved in the control of metabolism and at the same time is the organ that is first exposed to food-borne toxins or infectious agents, such insults could have profound metabolic effects. Notably, the microbiota of the gut can affect the control of energy metabolism; therefore, changes in the microbiota might contribute to the epidemic of obesity and T2DM [64].

Future studies are required to unravel the role of the gut in obesity and diabetes, but there is a strong rationale to consider the GI tract as a valuable target for future interventional therapies for obesity and diabetes.

Conclusion

Obesity is a major health disorder both in the developed and developing countries. In the past two decades, much knowledge has been gained about the pathophysiology of obesity as it relates to the mechanisms involved in regulation of appetite and energy homeostasis. A better understanding of the central and peripheral factors involved—particularly the role of gut hormones—will pave the way for development of improved treatment modalities for obesity.

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