A Skeletal Muscle-Derived Secretory Protein, Attractin, Upregulates UCP-2 Expression in Mouse 3T3-L1 Adipocytes
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Skeletal muscle is a major organ involved in the homeostasis of glucose and lipid metabolism. Here, we report that a muscle-derived secretory protein, attractin, highly expressed under unloading conditions, could regulate the expression of uncoupling protein-2 (UCP-2), which is a proton carrier that uncouples electron transport from ATP synthesis, in adipocytes. Attractin has two alternative splicing variants: membrane-bound and secreted forms. Since loss-of-function mutations in membrane-bound attractin decreases body weight by suppressing appetite in mice, we hypothesize that secreted-type attractin also could regulate energy homeostasis. We first showed that unloading conditions, such as spaceflight and tail-suspension, increased the amount of secreted-type attractin mRNA in rat gastrocnemius muscle. Next, co-culturing of attractin-overexpressing COS7 cells with 3T3-L1 adipocytes or L6 myotubes revealed that secreted-type attractin increased the amounts of UCP-2 mRNA and protein in 3T3-L1 adipocytes, but not in L6 myotubes. Secreted-type attractin failed to upregulate expression of UCP-1 and UCP-3 in 3T3-L1 adipocytes. Two-dimensional polyacrylamide gel electrophoresis also showed that expression of several proteins were up- or down-regulated in 3T3-L1 adipocytes co-cultured with attractin-overexpressing COS7 cells, whereas the profile of protein expression hardly changed in the co-cultured L6 myotubes, indicating that secreted-type attractin preferentially affects adipocytes more than myotubes. Our present study suggests that secreted-type attractin may function as an energy regulating factor in skeletal muscle by upregulating UCP-2 expression level in adipocytes.
- Biol. Sci. Space
Biol. Sci. Space 20(2), 33-39, 2006-11-01
Japanese Society for Biological Sciences in Space