Abnormal brown and white fat development in transgenic mice overexpressing glycerol 3-phosphate dehydrogenase

Abstract

Mice carrying ∼25 copies of a transgene encoding glycerol 3-phosphate dehydrogenase expressed from 50 to 200 times the level of enzyme produced by a single copy of the normal endogenous gene. The enzyme constituted >50% of the cytoplasmic protein in the brown fat of a transgenic mouse. Young transgenic mice (10 days to 8 weeks of age) appeared physically and reproductively normal; however, at the earliest times analyzed, the amount of brown fat of transgenic mice was greater than that of nontransgenic littermate controls. In contrast, the white fat depots, both subcutaneous and peritoneal, were severely reduced in size. Brown fat in transgenic mice also had larger lipid vacuoles and lower levels of Ucp mRNA, but Ucp mRNA levels were elevated in response to cold. Brown fat hypertrophy and reduction of white fat were particularly pronounced in aged transgenic animals. The results suggest that development of brown and white fat is altered by overexpression of glycerol 3-phosphate dehydrogenase.