LRP1 receptor controls adipogenesis and is up-regulated in human and mouse obese adipose tissue.
The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARgamma, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity.
Masson
Olivier
O
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM, U896, Université Montpellier1, CRLC Val d'Aurelle Paul Lamarque, Montpellier, France.
Chavey
Carine
C
Dray
Cédric
C
Meulle
Aline
A
Daviaud
Danielle
D
Quilliot
Didier
D
Muller
Catherine
C
Valet
Philippe
P
Liaudet-Coopman
Emmanuelle
E
D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
C434476:LRP1B protein, human; D008055:Lipids; C486644:Lrp1b protein, mouse; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins