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ENDOCRINE PHYSIOLOGY AND METABOLISM

Preadipocyte transplantation: an in vivo study of direct leptin signaling on adipocyte morphogenesis and cell size

¹Division of Molecular Genetics and ²Naomi Berrie Diabetes Center, Columbia University, New York, New York

Submitted 14 August 2008 ; accepted in final form 28 January 2009

Leptin has profound effects on adipose tissue metabolism. However, it remains unclear whether direct leptin signaling in adipocytes is involved. We addressed this question by transplanting inguinal adipose tissue stromal vascular cells (SVCs) from 4- to 5-wk-old wild-type (WT) and leptin receptor-deficient [Lepr^db/db (db)] mice to inguinal and sternal subcutaneous sites in Ncr nude mice. Both WT and db SVCs gave rise to mature adipocytes with normal morphologies 3 mo after the transplantation. The average adipocyte size (µm²/cell) was not significantly different between WT and db transplants at either the inguinal (1,630 ± 103 vs. 1,491 ± 74) or the sternal site (1,788 ± 107 vs. 1,596 ± 92). Expression levels of β₃-adrenergic receptor, a major mediator of lipid mobilization, were indistinguishable between WT and db transplants and similar to those of the hosts. Additionally, adipocyte sizes of inguinal transplants and endogenous inguinal adipose tissues were closely correlated (β = 0.76, P < 0.001), suggesting that the metabolic milieu of host mice has significant effects on adipocyte size of the transplants. Contrary to the indifference to donor's Lepr genotype, adipocyte size of the transplants was significantly affected by the donor's sex in a leptin receptor-dependent manner. In WT transplants, female SVCs gave rise to smaller adipocytes than male SVCs (1,358 ± 127 vs. 2,133 ± 171, P < 0.05). However, this sex difference was not significant in db transplants (1,537 ± 121 vs. 1,655 ± 140, P = 0.22). These data suggest that: 1) long-form receptor-mediated direct leptin signaling has no significant cell-autonomous effect on adipocyte differentiation and metabolism in adult mice, 2) sex may affect adipocyte metabolism via genetic and/or epigenetic programming, and 3) leptin may potentiate sexual dimorphism in adipocyte metabolism.

β₃-adrenergic receptor; sex; genetic and epigenetic programming; adipocyte progenitor cells; db mutation

This article has been cited by other articles:

				R. B. S. Harris Nature or nurture?: focus on "Preadipocyte transplantation: an in vivo study of direct leptin signaling on adipocyte morphogenesis and cell size" Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1336 - R1338. [Full Text] [PDF]