Obesity: Pathophysiology and Intervention

Abstract

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

Are Environmental Contaminants Responsible for ‘Globesity’?

“…The hypothalamus plays a crucial role for the central nervous system regulation of food intake, being a homeostatic control center for many other systems (i.e., reproduction and hormonal balances) [17]. Within the hypothalamus, a rich variety of neurotransmitters and peptide neuromodulators exist, and many of them participate in CNS control of appetite and food intake, food reward, or addiction [14,18].…”

“…The feedinginhibitory neurotransmitters (anorexogenic action) in the brain include the monoamines (in particular dopamine), serotonin (5-hydroxytryptamine, 5-HT), and a long list of gut-brain peptides [18].…”

“…Palatable foods can possibly activate the mesolimbic dopamine (DA) reward system. Hunger and satiety signals from adipose tissue, the pancreas, and the gastrointestinal tract relay the information about energy status through the neural hormonal gut-brain axis [18]. Obese humans express blunted striatal responses to palatable food [23].…”

The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

“…The last drug, Lorcaserin, is a selective serotonin 2C (5HT2c) receptor agonist (Yanovski and Yanovski, 2014). Lorcaserin stimulates pro-opiomelanocortin (POMC) release in the hypothalamus and thereby decreases appetite (Zhang et al, 2014).…”

NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression

“…It is known that obesity is a result of excessive accumulation of body fat,4 which is partly due to dysregulated adipogenesis. The differentiation and maturation of pre‐adipocytes are a complex process, in which a series of specific factors are involved.…”