Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell.
In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.
Lu
Zhao-Hui
ZH
Department of Endocrinology, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, PR China.
Mu
Yi-Ming
YM
Wang
Bao-An
BA
Li
Xie-Ling
XL
Lu
Ju-Ming
JM
Li
Jiang-Yuan
JY
Pan
Chang-Yu
CY
Yanase
Toshihiko
T
Nawata
Hajime
H
D000818:Animals; D017209:Apoptosis; D001095:Arachidonic Acids / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000494:pharmacology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D013229:Stearic Acids / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D001095:Arachidonic Acids; D002518:Ceramides; D005227:Fatty Acids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013229:Stearic Acids; D051028:bcl-2-Associated X Protein; D019308:Palmitic Acid; C031183:stearic acid