title: Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight.
abstract: Adiponectin is an adipocytokine with profound anti-diabetic and anti-atherogenic effects. Even though adiponectin expression is restricted to adipocytes, serum levels are paradoxically decreased in obesity. We characterized how adiponectin expression and regulation relates to adipocyte differentiation in a human adipocyte cell culture model. Adiponectin was not expressed by human preadipocytes. Differentiation into adipocytes was necessary to induce an increasing expression of adiponectin (359 +/- 64-fold, P < 0.001) in parallel to an increasing expression of adipocyte differentiation markers. Adiponectin protein synthesis and secretion occurred specifically in mature adipocytes and may thus serve as a distinctive marker of adipocyte differentiation. Addition of serum during the course of differentiation as well as acutely to mature adipocytes significantly and concentration-dependently suppressed adiponectin to almost non-detectable levels (to 9.8 +/- 0.03%, P = 0.0043), suggesting a strong humoral serum component of adiponectin down-regulation. This serum component is present in both obese and lean individuals with a tendency to a stronger effect in obese men and women. Separation by molecular size suggests that higher molecular weight (>30 kDa) fractions exert inhibition of adiponectin. Withdrawal of adipogenic ingredients from the culture medium also resulted in a decrease of adiponectin expression and secretion to 62.01 +/- 0.09% and 70.86 +/- 0.05%, respectively. We identified insulin as a critical component to maintain adiponectin expression with a down-regulation to 61.6 +/- 0.1% (P = 0.0011) in the absence of insulin. These dynamic changes of adiponectin expression and regulation with adipocyte differentiation are of physiological interest in the light of the paradoxical decrease of adiponectin levels and the continuous recruitment of preadipocytes for differentiation in obesity.
authors.affiliation: University Hospital for Children and Adolescents, University of Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Bertolt
authors.initials: B
authors.lastname: Seidel
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.forename: Antje
authors.initials: A
authors.lastname: Berthold
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D052242:Adiponectin / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D044967:Serum / Q000737:chemistry* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016895:Culture Media, Serum-Free; D007328:Insulin