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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

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      Endogenous n-3 polyunsaturated fatty acids (PUFAs) mitigate ovariectomy-induced bone loss by attenuating bone marrow adipogenesis in FAT1 transgenic mice

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          Abstract

          Aim

          To investigate the effect of endogenous n-3 polyunsaturated fatty acids (PUFAs) on bone marrow adipogenesis under osteoporosis conditions.

          Methods

          A mouse osteoporosis model overexpressing the FAT1 gene from Caenorhabditis elegans and converting n-6 PUFAs to n-3 PUFAs endogenously was used.

          Results

          The mice presented significantly lower bone marrow adiposity (adipocyte volume/tissue volume, mean adipocyte number) but increased the bone parameters (bone mineral density, bone mineral content, bone volume/total volume) in the distal femoral metaphysis.

          Conclusion

          Endogenous n-3 PUFAs protect bone marrow adipogenesis, which provides a novel drug target.

          Most cited references45

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          Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis.

          (1993)
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            Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis.

            J. Justesen, K Stenderup, E Ebbesen … (2001)
            Aging of the human skeleton is characterized by decreased bone formation and bone mass and these changes are more pronounced in patients with osteoporosis. As osteoblasts and adipocytes share a common precursor cell in the bone marrow, we hypothesized that decreased bone formation observed during aging and in patients with osteoporosis is the result of enhanced adipognesis versus osteoblastogenesis from precursor cells in the bone marrow. Thus, we examined iliac crest bone biopsies obtained from 53 healthy normal individuals (age 30-100) and 26 patients with osteoporosis (age 52-92). Adipose tissue volume fraction (AV), hematopoietic tissue volume fraction (HV) and trabecular bone volume fraction (BV) were quantitated as a percentage of total tissue volume fraction (TV) (calculated as BV + AV + HV) using the point-counting method. We found an age-related increase in AV/TV (r = 0.53, P < 0.001, n = 53) and an age-related decline in BV/TV (r = -0.46, P < 0.001, n = 53) as well as in the HV/TV (r -0.318, P < 0.05, n = 53). There was an age-related inverse correlation between BV/TV and AV/TV (r = -0.58, P < 0.001). No significant correlation between the AV/TV and the body mass index (r = 0.06, n.s., n = 52) was detectable. Compared with age-matched controls, patients with osteoporosis exhibited an increased AV/TV (P < 0.05) and decreased BV/TV (P < 0.05) but no statistically significant difference in HV/TV. Our data support the hypothesis that with aging and in osteoporosis an enhanced adipogenesis is observed in the bone marrow and that these changes are inversely correlated to decreased trabecular bone volume. The cellular and molecular mechanisms mediating these changes remain to be determined.
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              Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid.

              S K Fried, D Bunkin, A S Greenberg (1998)
              The purpose of this study was to determine whether human adipocytes from different depots of obese subjects produce interleukin-6 (IL-6) and whether IL-6 release is regulated by glucocorticoids. Fragments of omental and abdominal sc adipose tissue released immunodetectable IL-6 into the medium during acute incubations. Omental adipose tissue released 2-3 times more IL-6 than did sc adipose tissue. Isolated adipocytes prepared from these tissues also released IL-6 (omental > sc), but this accounted for only 10% of the total tissue release. Culture of adipose tissue fragments for 7 days with the glucocorticoid dexamethasone markedly suppressed IL-6 production. These data show for the first time that substantial quantities of IL-6 (up to 75 ng/mL) accumulate in the medium during incubations of both adipocytes and adipose tissue. Although little is known about the effects of IL-6 on adipose tissue, one action is a down-regulation of adipose tissue lipoprotein lipase. The regulated production of this multifunctional cytokine may modulate regional adipose tissue metabolism and may contribute to the recently reported correlation between serum IL-6 and the level of obesity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Title: Drug Design, Development and Therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1177-8881
                Publication date Collection: 2013
                Publication date (Electronic): 28 June 2013
                Volume: 7
                Pages: 545-552
                Affiliations
                [1 ]Department of Orthopaedic, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
                [2 ]Academy of Orthopaedics, Guangdong Province, Guangzhou, Guangdong, People’s Republic of China
                [3 ]Department of Dermatology and STD, Guangdong No.2 Provincial People’s Hospital, Guangzhou, Guangdong, People’s Republic of China
                [4 ]Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
                [5 ]Center of Metabolic Disease Research, Nanjing Medical University, Jiangsu, People’s Republic of China
                Author notes
                Correspondence: Xiao-chun Bai/Da-di Jin Department of Cell Biology, School of Basic Medical Science, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China, Tel +86 20 6164 8724, Fax +86 20 6164 8208, Email xiaochun_bai@ 123456163.com / baixc15@ 123456smu.edu.cn

                *These authors contributed equally to this work

                Article
                Publisher ID: dddt-7-545
                DOI: 10.2147/DDDT.S45263
                PMC ID: 3702224
                PubMed ID: 23843691
                SO-VID: e4c0168c-58c7-44cc-815c-4d56bbd15680
                Copyright © © 2013 Chen et al, publisher and licensee Dove Medical Press Ltd
                License:

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: antiosteoporosis,n-3 pufas,bone marrow,adipogenesis
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: antiosteoporosis, n-3 pufas, bone marrow, adipogenesis

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