Abstract
OBJECTIVE:
Phosphoinositide 3-kinase (PI3K) is required for murine adipocyte differentiation. However, a recent report concluded that PI3K was not involved in the differentiation of human preadipocytes into adipocytes. We have re-examined the role of PI3K in human preadipocyte differentiation, enrolling more patients and using more adipogenic indices.
METHODS:
Human preadipocytes, isolated from nine patients, were induced to differentiate in the presence or absence of 100 nM wortmannin. After 12–15 days, triacylglycerol accumulation and the expression of adipogenic markers (fatty acid synthase and adiponectin) were measured.
RESULTS:
A significant inhibition in triacylglycerol accumulation and in the induction of fatty acid synthase protein expression was observed, but there was no effect on adiponectin protein expression.
CONCLUSION:
Inhibition of PI3K reduces the differentiation of human preadipocytes into adipocytes, suggesting a role for this enzyme in the human adipogenic process.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Spiegelman BM, Flier JS . Obesity and the regulation of energy balance. Cell 2001; 104: 531–543.
Hegele RA, Leff T . Unbuckling lipodystrophy from insulin resistance and hypertension. J Clin Invest 2004; 114: 163–165.
Tomiyama K, Nakata H, Sasa H, Arimura S, Eisuke N, Watanabe Y . Wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, inhibits adipocytic differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 1995; 212: 263–269.
Sakaue H, Ogawa W, Matsumoto M, Kuroda S, Takata M, Sugimoto T, Spiegelman BM, Kasuga M . Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J Biol Chem 1998; 273: 28945–28952.
Patel NG, Holder JC, Smith SA, Kumar S, Eggo MC . Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. Diabetes 2003; 52: 43–50.
Gagnon A, Artemenko Y, Crapper T, Sorisky A . Regulation of endogenous SH2 domain-containing inositol 5-phosphatase (SHIP2) in 3T3-L1 and human preadipocyes. J Cell Physiol 2003; 197: 243–250.
Hauner H, Skurk T, Wabitsch M . Cultures of human adipose precursor cells. Methods Mol Biol 2001; 155: 239–247.
Cianflone K, Roncari DAK, Maslowska M, Baldo A, Forden J, Sniderman AD . Adipsin / acylation stimulation protein system in human adipocytes: regulation of triacylglycerol synthesis. Biochemistry 1994; 33: 9489–9495.
Gagnon A, Chen C-S, Sorisky A . Activation of protein kinase B and induction of adipogenesis by insulin in 3T3-L1 preadipocytes. Contribution of phosphoinositide-3,4,5-trisphosphate versus phosphoinositide-3,4-bisphosphate. Diabetes 1999; 48: 691–698.
Laemmli UK . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–685.
Gauthier B, Robb M, McPherson R . Cholesteryl ester transfer protein gene expression during differentiation of human preadipocytes to adipocytes in primary culture. Atherosclerosis 1999; 142: 301–307.
Varticovski L, Lu Z-R, Mitchell K, de Aos I, Kopecek J . Water-soluble HPMA copolymer–wortmannin conjugate retains phosphoinositide 3-kinase inhibitory activity in vitro and in vivo. J Controlled Rel 2001; 74: 275–281.
George S, Rochford JJ, Wolfrum C, Gray SL, Schinner S, Wilson JC, Soos MA, Murgatroyd PR, Williams RM, Acerini CL, Dunger DB, Barford D, Umpleby AM, Wareham NJ, Davies HA, Schafer AJ, Stoffel M, O'Rahilly S, Barroso I . A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science 2004; 304: 1325–1328.
Acknowledgements
This work was supported by a grant to AS from the Canadian Institutes of Health Research. AS is a Career Investigator of the Heart and Stroke Foundation of Ontario. AG is supported by a Premier's Research Excellence Award of Ontario awarded to AS.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aubin, D., Gagnon, A. & Sorisky, A. Phosphoinositide 3-kinase is required for human adipocyte differentiation in culture. Int J Obes 29, 1006–1009 (2005). https://doi.org/10.1038/sj.ijo.0802961
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0802961
Keywords
This article is cited by
-
Key circRNAs from goat: discovery, integrated regulatory network and their putative roles in the differentiation of intramuscular adipocytes
BMC Genomics (2023)
-
SHORT Syndrome: an Update on Pathogenesis and Clinical Spectrum
Current Diabetes Reports (2022)
-
APDS2 and SHORT Syndrome in a Teenager with PIK3R1 Pathogenic Variant
Journal of Clinical Immunology (2020)
-
Gene expression profile during proliferation and differentiation of rainbow trout adipocyte precursor cells
BMC Genomics (2017)
-
Simple surface engineering of polydimethylsiloxane with polydopamine for stabilized mesenchymal stem cell adhesion and multipotency
Scientific Reports (2015)