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 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-alpha). N-3 PUFA decreased secretion of non-induced IL-6 and TNF-alpha 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.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C077446:Pikasol; D016753:Interleukin-10; D020849:Raloxifene Hydrochloride; D002784:Cholesterol; C115121:LY 353381