Obesity is defined as a chronic disease in which body fat accumulation promotes adipose tissue dysfunction and results in many negative metabolic and psychosocial health consequences 
. According to the report from the World Health Organization in 2016, the prevalence of obesity and overweightness in adults reaches 39% worldwide and 73.6% in the United States. Unfortunately, obesity is a major risk factor for many diseases, notably type 2 diabetes (T2D), atherosclerosis, hypertension and cancer. These obesity-related diseases have resulted in annual medical costs in the United States reaching up to $147 billion US dollars. Due to the myriad of genetic and environmental factors that are involved in obesity, the therapeutic options that are advised by doctors are few in number. The major advices given to obese and overweight subjects include dietary control and exercise, however, these methods can be very difficult for the subjects and can result in multiple instances of relapse. Moreover, bariatric surgery is an alternative intervention method for obese people by altering gut hormone levels that are responsible for hunger and satiety. This surgery causes significant long-term weight loss, improvements in cardiovascular and diabetic risk factors and a reduction in mortality from 40% to 23% 
. However, this invasive surgery has been reported to cause adverse effects such as Dumping syndrome, bowel obstruction and complications due to the rapid weight loss. In order to contain this increasingly spreading epidemic, it is beneficial to find therapeutic options that can improve conditions of obese subjects around the world.
There are two types of adipose tissues in the human body including brown adipose tissue (BAT) and white adipose tissue (WAT). BAT is characterized by having multiple, smaller lipid droplets and containing many more mitochondria in comparison to WAT. This allows brown adipocytes to burn energy via thermogenesis. The primary gene product involved in thermogenesis is uncoupling protein 1 (UCP1). UCP1 is exclusively expressed in BAT and works by uncoupling oxidative phosphorylation from mitochondrial respiration, which results in heat production 
. Additionally, BAT displays a great ability to uptake substantial amounts of circulating free fatty acids and glucose as fuels for thermogenesis, which results in energy consumption within the body 
White adipocytes are characterized by a large unilocular lipid droplet that inhibits most of the space in the cell and possesses much fewer mitochondria. White adipocytes are responsible for storing energy within the body in the form of triglycerides and are commonly expanded in obese subjects. Two major types of WAT, which are subcutaneous and visceral white fats, can be found beneath the skin and surrounds the internal organs, respectively. Visceral white fats have been suggested to be associated with the risk of T2D and cardiovascular disease. Subcutaneous white fats are potentially able to be induced to acquire the features and thermogenic functions of BAT, which are termed as beige or brown-like adipocytes. Converting white to beige adipocytes, which is also known as the beiging or browning process, can be stimulated by cold acclimation, exercise training or pharmacologic activation of the β-adrenergic receptors 
. Two possible models for beige adipocytes formation have been established. Beige adipocytes can form via reprogramming of white mature adipocytes (transdifferentiation) or through de novo differentiation of resident progenitors within the WAT.
Thermogenic adipocytes including brown and beige adipocytes are previously considered non-existent in adult humans. However, this concept was later modified when studies had demonstrated that active thermogenic adipocytes are actually present in adult humans. Using positron emission tomography (PET) and computed tomography (CT) scanning, the areas of thermogenic adipocytes show the significant presence of 18
F-FDG), indicating high glucose uptake 
. Additionally, it has been found that cold exposure increases BAT activation and WAT browning in the body, resulting in increased thermogenesis 
Given the role of thermogenic adipocytes in energy expenditure and modulation of glucose and lipid metabolism and its crosstalk with other tissues, thermogenic adipocytes have been considered a promising therapeutic target to combat obesity and metabolic disorders. Overweight and obese subjects were found to have decreased thermogenic adipocytes activity in comparison to lean and healthy subjects 
. Several studies have demonstrated that increasing the amount and activity of thermogenic adipocytes improves metabolism in mouse models of obesity or diabetes 
. Cold-activated or drugs-activated thermogenic adipocytes can also improve insulin sensitivity and glucose tolerance in healthy subjects and patients with T2D 
. From the translational point of view, we focus on the therapeutic potential of activating thermogenic function or converting white to thermogenic adipocytes in human subjects or human cells by genetic, pharmacological and cell-based approaches (Figure 1
Figure 1. Cell-based, gene-based and pharmacological therapies to increase thermogenic adipocytes in obese subjects. In pharmacological therapies, several compounds, proteins, lipids or metabolites have been applied for treatment of obesity through the regulation of thermogenic adipocytes activity and energy expenditure. In gene therapy, the delivery of DNA (transgene), mRNA, microRNA, or Cas9/gRNA system can be used to modulate the expression of genes involved in the thermogenic pathway. Cell-based therapies include autologous and allergenic cell therapies depending on the source of the transplanted cells. Precursor cells isolated from obese subjects (autologous) or healthy donors (allergenic) can be engineered and differentiated to thermogenic adipocytes followed by transplantation of the fat back to the obese subjects.