Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells

Yi Ming Mu, Toshihiko Yanase, Yoshihiro Nishi, Atsushi Tanaka, Masayuki Saito, Cheng Hao Jin, Chizu Mukasa, Taijiro Okabe, Masatoshi Nomura, Kiminobu Goto, Hajime Nawata

Research output: Contribution to journalArticle

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Abstract

Obesity is associated with insulin resistance and some reproductive abnormalities. Circulating FFAs are often elevated in obese subjects and are also closely linked to insulin resistance. In this study, we demonstrated that saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated FFA, arachidonic acid, had no effect on the cell survival, even at supraphysiological concentrations. The suppressive effect of saturated FFAs on cell survival was caused by apoptosis, as evidenced by DNA ladder formation and annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of palmitic acid and stearic acid were unrelated to the increase of ceramide generation or nitric oxide production and were also completely blocked by Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was consistent with the effect of the respective FFA form. Surprisingly, arachidonic acid instead showed a protective effect on palmitic acid- and stearic acid-induced cell apoptosis. A Western blot analysis showed the apoptosis of the granulosa cells induced by palmitic acid to be accompanied by the down-regulation of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector, Bax. These results indicate that saturated FFAs induce apoptosis in human granulosa cells caused by the metabolism of the respective acylcoenzyme A form, and the actual composition of circulating FFAs may thus play a critical role in the apoptotic events of human granulosa cells. These effects of FFAs on granulosa cell survival may be a possible mechanism for reproductive abnormalities, such as amenorrhea, which is frequently observed in obese women.

Original languageEnglish
Pages (from-to)3590-3597
Number of pages8
JournalEndocrinology
Volume142
Issue number8
DOIs
Publication statusPublished - Jan 1 2001

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Palmitic Acid
Granulosa Cells
Cell Survival
Apoptosis
Arachidonic Acid
Insulin Resistance
Propidium
Ceramides
Annexin A5
Amenorrhea
Ligases
stearic acid
Nitric Oxide
Up-Regulation
Down-Regulation
Obesity
Western Blotting
Staining and Labeling
DNA

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Mu, Y. M., Yanase, T., Nishi, Y., Tanaka, A., Saito, M., Jin, C. H., ... Nawata, H. (2001). Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. Endocrinology, 142(8), 3590-3597. https://doi.org/10.1210/endo.142.8.8293

Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. / Mu, Yi Ming; Yanase, Toshihiko; Nishi, Yoshihiro; Tanaka, Atsushi; Saito, Masayuki; Jin, Cheng Hao; Mukasa, Chizu; Okabe, Taijiro; Nomura, Masatoshi; Goto, Kiminobu; Nawata, Hajime.

In: Endocrinology, Vol. 142, No. 8, 01.01.2001, p. 3590-3597.

Research output: Contribution to journalArticle

Mu, YM, Yanase, T, Nishi, Y, Tanaka, A, Saito, M, Jin, CH, Mukasa, C, Okabe, T, Nomura, M, Goto, K & Nawata, H 2001, 'Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells', Endocrinology, vol. 142, no. 8, pp. 3590-3597. https://doi.org/10.1210/endo.142.8.8293
Mu, Yi Ming ; Yanase, Toshihiko ; Nishi, Yoshihiro ; Tanaka, Atsushi ; Saito, Masayuki ; Jin, Cheng Hao ; Mukasa, Chizu ; Okabe, Taijiro ; Nomura, Masatoshi ; Goto, Kiminobu ; Nawata, Hajime. / Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. In: Endocrinology. 2001 ; Vol. 142, No. 8. pp. 3590-3597.
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AU - Saito, Masayuki

AU - Jin, Cheng Hao

AU - Mukasa, Chizu

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