INDEPENDENT REGULATION OF ADIPOSE TISSUE-SPECIFICITY AND OBESITY RESPONSE OF THE ADIPSIN PROMOTER IN TRANSGENIC MICE

Transcription of the adipocyte specific adipsin gene is dramatically r educed in the adipose tissue of a number of genetically and chemically -induced obese rodents. To map the region of the adipsin gene that con fers this response to obesity transgenic mice were made containing -11 4, -250, -400, -700, and -938 base pairs (bp) to +35 bp of the promote r linked to the bacterial chloramphenicol acetyltransferase gene. Tran sgenic mice containing as few as 114 bp of the adipsin promoter had hi gh levels of chloramphenicol acetyltransferase activity in adipose tis sue. However, only those mice with 938 bp of the adipsin upstream regu latory region showed suppression of expression in adipose tissue in mi ce that were induced to become obese with monosodium glutamate. Using gel retardation assays, we showed that a 56-bp fragment of DNA mapping between -687 and -743 bp upstream from the start of adipsin expressio n was bound by protein factors in nuclear extracts prepared from adipo se tissue. There was much greater retardation of this fragment with nu clear extracts prepared from adipose tissue of lean versus obese mice. These results indicate that a tissue-specific transcription factor(s) that regulates adipsin expression is less active in the adipose tissu e of obese animals.