Cellular bioenergetics as a target for obesity therapy

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Adaptive thermogenesis, defined as the heat produced in response to environmental temperature or diet, can be divided into three subtypes. Cold exposure induces shivering thermogenesis, a function of skeletal muscle, and non-shivering thermogenesis, a function of brown fat. Overfeeding triggers diet-induced thermogenesis; this is also a function of brown fat. Recent studies using positron emission tomography (PET) and computed tomography (CT) imaging prove that adult humans possess physiologically active uncoupled protein 1 (UCP1)-positive brown fat, leading to the consideration within the medical and scientific communities that brown fat may play a part in normal physiology and could be a target for obesity treatment. There are at least two types of brown fat cells located in different anatomical locations in mice, each arising from different developmental origins. Compared with the preformed interscapular brown fat cells, the systemic brown fat cells, found in white fat and between muscle bundles, are often found admixed with white adipocytes; are more sensitive to β3-adrenergic receptor stimulation and cold exposure; and have a thermogenic capacity that seems to be regulated by genetic background. The contribution of the two different populations of progenitors to adult human brown fat remains to be determined. Three types of thermogenesis occur in skeletal muscle: exercise-induced thermogenesis, non-exercise activity thermogenesis, and cold-induced shivering thermogenesis. Thus, therapeutic interventions that mimic these mechanisms could potentially increase the thermogenic capacity of muscle and counteract obesity. This is especially beneficial to individuals with physical limitations in exercising or to those who are genetically predisposed to obesity. Based on the current knowledge of bioenergetics, four potential therapeutic approaches could be envisioned: increasing brown fat differentiation from progenitor cells; activating brown fat thermogenesis; promoting skeletal muscle thermogenesis; or increasing general mitochondrial uncoupling.