Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts

Abstract

Obesity represents an abnormal fat accumulation resulting from energy imbalances. It represents a disease with heavy consequences on population health and society economy due to its related morbidities and epidemic proportion. Defining and classifying obesity and its related parameters of evaluation is the first challenge toward understanding this multifactorial health problem. Therefore, within this review we report selected illustrative examples of the underlying mechanisms beyond the obesity pathogenesis which is systemic rather than limited to fat accumulation. We also discuss the gut-brain axis and hormones as the controllers of energy homeostasis and report selected impacts of obesity on the key metabolic tissues. The concepts of "broken energy balance" is detailed as the obesity starting key step. Sleep shortage and psychological factors are also reported with influences on obesity development. Importantly, describing such mechanistic pathways would allow clinicians, biologists and researchers to develop and optimize approaches and methods in terms of diagnosis, classification, clinical evaluation, treatment and prognosis of obesity.

Keywords: energy misbalance; homeostatic mechanisms; obesity; pathogenesis; therapy; “broken energy balance”.

Figure 1

Different fat distribution patterns with diverse outcomes.

Figure 2

Theory of obesity establishment despite the existence of mechanisms balancing the energy homeostasis. An unhealthy lifestyle (inactivity, unhealthy diet, sleep shortage and psychological disorders) puts pressure on the energy homeostasis balance and breaks it, which leads to obesity development. Once obesity established, the mechanisms of energy balance are blunted, and the brain sets an increased body weight as a new reference, which makes correcting obesity difficult (biological pathways resist weight loss).

Figure 3

Sleeping, psychology and obesity.