Effects of long-term administration of N-3 polyunsaturated fatty acids (PUFA) and selective estrogen receptor modulator (SERM) derivatives in ovariectomized (OVX) mice

We studied the beneficial effects of dietary consumption of n‐3 polyunsaturated fatty acids (PUFA) and two selective estrogen receptor modulator (SERM) derivatives (SERM‐I and SERM‐II) and their combined effect on serum lipids, skin dermis and adipose layers, bone marrow adipogenesis, and cytokine s...

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Veröffentlicht in:Journal of cellular biochemistry 2003-10, Vol.90 (2), p.347-360
Hauptverfasser: Zeitlin, L., Segev, E., Fried, A., Wientroub, S.
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Sprache:eng
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Zusammenfassung:We studied the beneficial effects of dietary consumption of n‐3 polyunsaturated fatty acids (PUFA) and two selective estrogen receptor modulator (SERM) derivatives (SERM‐I and SERM‐II) and their combined effect on serum lipids, skin dermis and adipose layers, bone marrow adipogenesis, and cytokine secretion in mice. Two different ovariectomized (OVX) models were studied: treatment began immediately post‐OVX in one and 3 months post‐OVX in the other. Our results showed that n‐3 PUFA and both SERMs decreased triglyceride levels in the serum, and that SERMs also decreased serum cholesterol levels while n‐3 PUFA had no similar effect. SERMs had no effect on IL‐6, IL‐1 beta, or IL‐10 levels, but they decreased ex vivo tumor necrosis factor (TNF‐α). N‐3 PUFA decreased secretion of non‐induced IL‐6 and TNF‐α from cultured BMC and IL‐1 beta levels in vivo (i.e., in bone marrow plasma), but its main effect was a significant elevation in the secretion of IL‐10, a known anti‐inflammatory cytokine. OVX‐induced B‐lymphopoiesis was not affected by LY‐139481 (SERM‐I) while LY‐353381 (SERM‐II) exhibited an estrogen‐antagonistic effect in sham and OVX mice and elevated the amount of B‐cells in bone marrow. Fish oil consumption prevented the elevation in B‐lymphopoiesis caused by OVX, but had no curative effect on established augmented B‐lymphopoiesis. This activity could be mediated via the elevation of IL‐10 which was shown to suppress B‐lymphopoiesis. Both SERMs and n‐3 PUFA inhibited the increase in adipose tissue thickness caused by OVX in mice. Our results showed that n‐3 PUFA, could prevent some of the deleterious outcomes of estrogen deficiency that were not affected by SERMs. We observed no significant beneficial effects of the combined administration of SERM‐I, SERM‐II, and PUFA on the studied parameters.The exact mechanism by which polyunsaturated fatty acids exert their activities is still not clear, but peroxisome proliferator‐activated receptors (PPARs) might be involved in processes which are modulated by n‐3 PUFA. J. Cell. Biochem. 90: 347–360, 2003. © 2003 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.10620