Adipose tissue cellularity and apoptosis after intracerebroventricular injections of leptin and 21 days of recovery in rats
2003
Gullicksen, P.S. | Hausman, D.B. | Dean, R.G. | Hartzell, D.L. | Baile, C.A.
OBJECTIVE: To determine the effect of leptin and post-treatment recovery on adipose tissue cellularity and apoptosis. In addition, to investigate whether Bcl-2 and/or Bax is involved in the mechanism of leptin-induced adipose tissue apoptosis. DESIGN: A total of 24 adult male Sprague–Dawley rats were injected i.c.v. with either 10 μg mouse leptin or 10 μl vehicle once per day for 4 days. At 24 h after the last injection, one group was killed while the other was monitored for 21 days. MEASUREMENTS: DNA fragmentation and Bcl-2 and Bax protein levels were determined in inguinal (ING), epididymal (EPI) and retroperitoneal (RP) white adipose tissues and the interscapular brown adipose tissue (BAT). Cellularity was determined in ING and EPI. RESULTS: Leptin significantly reduced the masses of all white fat pads [RPINGEPI] but not BAT. Cell volume was significantly reduced in EPI and ING. Only ING had a significantly reduced cell number from leptin treatment plus exhibited apoptosis by increased DNA fragmentation and DNA laddering, and upregulation of pro-apoptosis Bax protein. The other fat pads exhibited a general trend to increase the Bcl-2/Bax ratio. Recovery allowed for normalization of white fat pad mass, cell number and cell volume; however, BAT mass increased 42% over control. After recovery, apoptosis was not detected, Bcl-2 protein had increased in ING, and the Bcl-2/Bax ratio had risen overall. CONCLUSIONS: Central administration of mouse leptin in the rat targets white fat depots individually to reduce mass by a reduction in cell volume plus adipocyte deletion in, at least, the ING fat pad by Bax-mediated apoptosis. Even after a dramatic loss in adipose tissue mass and change in cellularity, the rat demonstrates a resilient return to control levels together with an increase in factors that prevent adipocyte loss.
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