Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype

In mammals, two types of adipose tissue are present, brown and white. They develop sequentially, as brown fat occurs during late gestation whereas whi te fat grows mainly after birth. However, both tissues have been shown to h ave great plasticity. Thus an apparent transformation of brown fat into whi te fat takes place during post-natal development. This observation raises q uestions about a possible conversion of brown into white adipocytes during development, although indirect data argue against this hypothesis. To inves tigate such questions in vivo, we generated two types of transgenic line. T he first carried a transgene expressing Cre recombinase specifically in bro wn adipocytes under the control of the rat UCP1 promoter. The second corres ponded to an inactive lacZ gene under the control of the human cytomegalovi rus promoter. This dormant gene is inducible by Cre because it contains a S top sequence between two loxP sequences, separating the promoter from the c oding sequence. Adipose tissues of progeny derived by crossing independent lines established from both constructs were investigated. LacZ mRNA corresp onding to the activated reporter gene was easily detected in brown fat and not typically in white fat, even by reverse transcriptase PCR experiments. These data represent the first direct experimental proof that, during norma l development, most white adipocytes do not derive from brown adipocytes.