Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity.

J Clin Invest 1995 Dec;96(6):2914-23

Jackson Laboratory, Bar Harbor, Maine 04609, USA.

The brown fat-specific mitochondrial uncoupling protein (UCP) provides a mechanism for generating heat by uncoupling respiration and oxidative phosphorylation. It has been suggested that this system of thermogenesis can provide a defense against obesity. To test this idea, we created a transgenic mouse in which the fat-specific aP2 gene promoter directed Ucp expression in white fat and provided for the constitutive expression of Ucp in brown fat. Transgenic mice showed both Ucp mRNA and immunoreactive UCP in white fat at 2-10% the level normally measured in brown fat. A reduction in subcutaneous fat of aP2-Ucp C57BL/6J mice was observed at 3 mo of age. When the transgene was expressed in Avy genetically obese mice reductions in total body weight and subcutaneous fat stores were observed. Female transgenic Avy mice at 13 mo of age weighed 35 grams, a weight indistinguishable from nontransgenic C57BL/6J mice. Gonadal fat showed an increase in a novel adipocyte derivative that did not accumulate lipids and that constituted approximately 80% of the mass of the tissue in Avy transgenic. A major effect of aP2-Ucp in brown fat was to reduce endogenous gene expression by as much as 95%. The results suggest that UCP synthesized from the aP2 gene promoter is thermogenically active and capable of reducing fat stores.

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI118363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC186003PMC
December 1995
2 Reads

Publication Analysis

Top Keywords

gene promoter
12
ap2 gene
12
brown fat
12
fat
9
white fat
8
c57bl/6j mice
8
uncoupling protein
8
subcutaneous fat
8
mitochondrial uncoupling
8
fat stores
8
ucp
6
gene
5
mice
5
obese mice
4
avy genetically
4
expressed avy
4
mice reductions
4
genetically obese
4
weight subcutaneous
4
observed female
4

Altmetric Statistics

Similar Publications