Abstract
The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%–4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.
Highlights
Age-associated bone loss is an eloquent and widespread, health and socioeconomic burden among a fast-growing aging population
We examined if the RANKL stimulated activation of NF-κB, Jun N terminal kinase (JNK), and p38 mitogen activated protein kinase (MAPK) in bone marrow (BM) cells was modulated by concentrated fish oil (CFO)
We have previously reported that a diet containing 9% regular fish oil (FO) (EPA/docosahexaenoic acid (DHA), 18%/12%) could prevent bone loss during aging [13]
Summary
Age-associated bone loss is an eloquent and widespread, health and socioeconomic burden among a fast-growing aging population. Studies reveal that around 50% of women over the age of 50, and 1 out of 4 men, will experience osteoporotic bone fracture [1]. Increased fracture risks are the major concerns of the aging process and imply new and immediate prevention strategies. The underlying causes for the age-related increase in bone fractures are not clear yet; bone resorption seems to play a major role. Despite the unknown etiology of age-related bone loss, one prominent feature is a chronic inflammation reaction driven, in part, by increased pro-inflammatory cytokine expression that contributes to the pathogenesis of the disease. Bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts) are systematically
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