Abstract: Non-naturally occurring thermogenic adipocytes are provided. The cells have a distinctive molecular signature, and can be distinguished from predecessor cells such as adipose-derived stem cells as well as other naturally occurring and induced thermogenic cells. Differentiation media that can induce differentiation of ADSC and white adipocytes into thermogenic adipocytes is also provided. Methods of making thermogenic adipocytes, thermogenic adipocytes made according the disclosed methods as well as conditioned media made according a method of incubating the cells in a tissue culture media are also provided. Compositions including thermogenic adipocytes, conditioned media, secreted factor(s), active agents that increase the number or activity of thermogenic adipocytes, or a combination thereof are also disclosed and can be used to treat a variety of diseases and conditions, particularly obesity and metabolic disorders.