Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal.

Growth hormone (GH) receptor knockout (GHRKO) mice are highly insulin sensitive and long-lived. Surgical visceral fat removal (VFR) improves insulin signaling in normal mice and rats and extends longevity in rats. We have previously demonstrated decreased expression of certain pro-apoptotic genes in kidneys of GHRKO mice and suggested that this could contribute to the increased longevity of these animals. The aim of the present study was to examine the level of the following proteins: caspase-3, caspase-9, caspase-8, bax, bad, phospho-bad, bcl-2, Smac/DIABLO, Apaf-1, phospho-p53 (pp53) and cytochrome c in male GHRKO and normal (N) mice subjected to VFR or sham surgery, at approximately six months of age. The kidneys were collected two months after VFR. Caspase-3, caspase-8, bax, bad, Smac/DIABLO, Apaf-1 and pp53 levels were decreased in GHRKO mice as compared to N animals. VFR did not change the level of any of the examined proteins. The decreased renal levels of pro-apoptotic proteins could contribute to the extended life-span caused by targeted disruption of the GH receptor gene but are apparently not involved in mediating the effects of VFR.