Tumor necrosis factor-alpha-induced adipose-related protein (TIARP), a cell-surface protein that is highly induced by tumor necrosis factor-alpha andadipose conversion

Tumor necrosis factor-alpha (TNF alpha) is involved in the physiological an d biological abnormalities found in two opposite metabolic situations: cach exia and obesity. In an attempt to identify novel genes and proteins that c ould mediate the effects of TNFa alpha on adipocyte metabolism, and develop ment, we have used a differential display technique comparing 3T3-L1 cells exposed or not to the cytokine. We have isolated a novel adipose cDNA encod ing a TNF alpha -inducible 470-amino acid protein termed TIARP, with six pu tative transmembrane regions flanked by a large amino-terminal and a short carboxyl-terminal domain, a structure reminiscent of channel and transporte r proteins. Commitment into the differentiation process is required for cyt okine responsiveness. The differentiation process per se is accompanied by a sharp emergence of TIARP m-RNA transcripts, in parallel with the expressi on of the protein at the plasma membrane. Transcripts are present at high l evels in white and brown adipose tissues, and are also detectable in liver, kidney, heart, and skeletal muscle. Whereas the biological function of TIA RP is presently unknown, its pattern of expression during adipose conversio n and in response to TNF alpha exposure as a transmembrane protein mainly l ocated at the cell surface suggest that TIARP might participate in adipocyt e development and metabolism and mediate some TNF alpha effects on the fat cell as a channel or a transporter.