title: Recombinant human FIZZ3/resistin stimulates lipolysis in cultured human adipocytes, mouse adipose explants, and normal mice.
abstract: Human FIZZ3 (hFIZZ3) was identified as an ortholog of mouse resistin (mResistin), an adipocyte-specific secreted factor linked to insulin resistance in rodents. Unlike mResistin, hFIZZ3 is expressed in macrophages and monocytes, but is undetectable in adipose tissue. The profound macrophage infiltration of adipose that occurs during obesity suggests that hFIZZ3 may play an important role in adipocyte biology. Using a recombinant protein produced in Escherichia coli, we report here that chronic treatment of cultured human adipocytes with hFIZZ3 results in hypotropic cells with smaller lipid droplets. Recombinant hFIZZ3 facilitates preadipocyte proliferation and stimulates adipocyte triglyceride lipolysis, whereas recombinant mResistin inhibits adipocyte differentiation, with no detectable effect on proliferation or lipolysis. In addition, insulin-stimulated glucose uptake and Akt phosphorylation are not altered in hFIZZ3-treated adipocytes, indicating an intact insulin response. In mouse adipose explants, hFIZZ3 accelerates simultaneously triglyceride lipolysis and fatty acid reesterification, as assessed by measurement of glycerol and fatty acid release. Consistent with the in vitro findings, acute administration of recombinant hFIZZ3 into normal mice caused a significant increase in serum glycerol concentration with no elevation in free fatty acid at 45 min post injection. Taken together, the data suggest that recombinant hFIZZ3 can influence adipose metabolism by regulating preadipocyte cell number, adipocyte lipid content, and energy expenditure via accelerating the fatty acid/triglyceride futile cycle.
authors.affiliation: CuraGen Corp., Branford, Connecticut 06405, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ort
authors.forename: Anibal A
authors.initials: AA
authors.lastname: Arjona
authors.forename: John R
authors.initials: JR
authors.lastname: MacDougall
authors.forename: Pam J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Mark E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Wu
authors.forename: Andrew
authors.initials: A
authors.lastname: Eisen
authors.forename: Yuan-Di C
authors.initials: YD
authors.lastname: Halvorsen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006729:Hormones, Ectopic / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000494:pharmacology*; D052243:Resistin; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D006729:Hormones, Ectopic; D007328:Insulin; D011518:Proto-Oncogene Proteins; C499624:RETN protein, human; D011994:Recombinant Proteins; D052243:Resistin; C499623:Retn protein, mouse; D014280:Triglycerides; C482058:resistin-like gamma, mouse; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D005990:Glycerol