Primary Causes of Adipose Tissue Weight Gain

Excess adipose tissue accumulation (obesity) results from excess caloric intake relative to the body’s energy expenditure. There are potentially numerous causes of obesity involving defects in regulating food intake and/or energy expenditure. Monogenic obesity is caused by single gene defects and is usually characterized by severe and early-onset obesity. Syndromic obesity may be caused by a single gene defect or defects in multiple functionally unrelated genes as a result of chromosomal deletion, rearrangement, and/or imprinting. Syndromic obesity usually occurs early in life as one of the multiple phenotypic manifestations characteristic of the syndromes. While monogenic and syndromic obesities are rare, a large percentage of the human population develops common forms of obesity when they are persistently exposed to an obesogenic environment. Susceptible individuals have a permissive genetic background, which may involve tens and even hundreds of gene variants, that predisposes them to excess food intake and/or relatively decreased energy expenditure. Food intake is regulated by metabolic signals to satisfy one’s energy needs and by hedonic signals based on one’s pleasure/reward needs; derangement in either could lead to excessive caloric intake and obesity. Classifying the common forms of obesity into metabolic obesity, caused by disorders in the metabolic signaling pathways that lead to an elevated but homeostatically regulated body weight, versus hedonic obesity, caused by disorders in the reward system that result in sustained hedonic overeating above the metabolic needs, should aid the better use of the available treatment modalities and the development of more effective treatments in the future.