Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese

Abstract

The prevalence of obesity is increasing and with it the prevalence of associated metabolic complications. Precisely how obesity results in metabolic disturbances remains unclear. In the face of persistent positive caloric balance, it has been postulated that the capacity of adipose tissue to safely store fat may be vital. This paper explores some of the evidence suggesting that the risk of developing metabolic disturbances is not related to how much fat an individual has, but how well their fat can expand to accommodate the caloric excess. If this is true, the metabolic consequences of obesity may arise from the inability to become more obese.

Adipose tissue in control of metabolism

“…White adipocytes are mainly present in WAT with variable size (25-200 μm) and have a unilocular lipid droplet, few mitochondria and a low oxidative rate (Jeanson et al 2015). In line with this, white adipocytes have high capacity of storing energy in the form of TGs, and protect organs such as muscle and liver from lipotoxicity (Tan & Vidal-Puig 2008). Although white adipocytes arise from resident cells of mesenchymal origin in white fat, subcutaneous adipocytes have distinct developmental origins and metabolic properties from visceral adipocytes in rodents and humans (Laviola et al 2006, Ibrahim 2010, Berry et al 2013, Chau et al 2014.…”

“…The surplus energy is efficiently deposited in the form of neutral triglycerides (TGs) in adipose tissue through the lipogenic pathway. However, the storage of neutral TGs in adipocytes increases the lipid droplet size, which results in adipose expansion and subsequent obesity (Tan & Vidal-Puig 2008). By contrast, TGs reserved in adipocytes are broken down into glycerol and fatty acids through lipolytic pathway when food is scarce, energy expenditure requirements are stimulated or the storage of neutral TGs exceeds the capacity of adipocytes (Lafontan & Langin 2009).…”

Obesity and related consequences to ageing

“…The expandability hypothesis states that when AT reaches its capacity to store fat, insulin sensitivity deteriorates (Tan and Vidal-Puig 2008). When adipose depot of an individual is not able to expand further to store excess energy, then ectopic lipid accumulation occurs, which as a consequence can lead to insulin resistance or cardiovascular complications.…”

Role of Fat Body Lipogenesis in Protection against the Effects of Caloric Overload in Drosophila

“…HSD-reared larvae contain a larger pool of stored lipids midway through development than controls such that their capacity to further store lipids may be compromised (Table 1). Growing evidence in other models suggests that storage of excess NEFA in adipose TAG may be protective against T2D, an idea that challenges the current paradigm that obesity causes T2D (57,58). Increasing fat storage in adipose tissue protects mice from T2D (59,60), and animals that cannot store fat normally are insulin-resistant when fed normal diets (61,62).…”