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Chondroprotection of leptin deficiency demystified?

  • V.B. Kraus
    Correspondence
    Address correspondence and reprint requests to: V.B. Kraus, Duke Molecular Physiology Institute, Box 104775, 300 North Duke St, Durham, NC, 27701, USA. Tel.: 1-919-681-6652; fax: 1-919-684-8907
    Affiliations
    Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, NC, USA
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  • A.E. Nelson
    Affiliations
    Thurston Arthritis Research Center and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • Z. Huang
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China
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Published:October 12, 2022DOI:https://doi.org/10.1016/j.joca.2022.10.006
      Using the unique preclinical model of lipodystrophy—a rare heterogeneous disorder characterized by the absence of subcutaneous adipose tissue—paracrine signaling from fat, rather than body weight, has been identified as a mediator of spontaneous and injury-induced joint degeneration
      • Collins K.H.
      • Lenz K.L.
      • Pollitt E.N.
      • Ferguson D.
      • Hutson I.
      • Springer L.E.
      • et al.
      Adipose tissue is a critical regulator of osteoarthritis.
      . Lipodystrophy is a leptin-deficient state that can be considered a lipid-partitioning disorder associated with severe insulin resistance, fatty liver, and hyperlipidemia (www.endotext.org). Other leptin-deficient states associated with extreme obesity are also chondroprotective, including deficiency due to a leptin gene mutation, as observed in ob/ob mice
      • Griffin T.
      • Huebner J.
      • Kraus V.
      • Guilak F.
      Extreme obesity due to impaired leptin signaling in mice does not increase knee osteoarthritis.
      , functional deficiency due to a leptin receptor gene mutation or silencing, as observed in db/db mice
      • Griffin T.
      • Huebner J.
      • Kraus V.
      • Guilak F.
      Extreme obesity due to impaired leptin signaling in mice does not increase knee osteoarthritis.
      , and lentiviral vector-mediated leptin receptor targeting
      • Deng J.
      • Liu Y.
      • Yang M.
      • Wang S.
      • Zhang M.
      • Wang X.
      • et al.
      Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response.
      .

      Keywords

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      References

        • Collins K.H.
        • Lenz K.L.
        • Pollitt E.N.
        • Ferguson D.
        • Hutson I.
        • Springer L.E.
        • et al.
        Adipose tissue is a critical regulator of osteoarthritis.
        Proc Natl Acad Sci USA. 2021; : 118
        • Griffin T.
        • Huebner J.
        • Kraus V.
        • Guilak F.
        Extreme obesity due to impaired leptin signaling in mice does not increase knee osteoarthritis.
        Arthritis Rheum. 2009; 60: 2935-2944
        • Deng J.
        • Liu Y.
        • Yang M.
        • Wang S.
        • Zhang M.
        • Wang X.
        • et al.
        Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response.
        Arthritis Rheum. 2012; 64: 3564-3573
        • Cordero-Barreal A.
        • González-Rodríguez M.
        • Ruiz-Fernández C.
        • Eldjoudi D.A.
        • AbdElHafez Y.R.F.
        • Lago F.
        • et al.
        An update on the role of leptin in the immuno-metabolism of cartilage.
        Int J Mol Sci. 2021; : 22
        • Zou W.
        • Rohatgi N.
        • Brestoff J.R.
        • Zhang Y.
        • Scheller E.L.
        • Craft C.S.
        • et al.
        Congenital lipodystrophy induces severe osteosclerosis.
        PLoS Genet. 2019; 15e1008244
        • Ait Eldjoudi D.
        • Cordero Barreal A.
        • Gonzalez-Rodríguez M.
        • Ruiz-Fernández C.
        • Farrag Y.
        • Farrag M.
        • et al.
        Leptin in osteoarthritis and rheumatoid arthritis: player or bystander?.
        Int J Mol Sci. 2022; 23
        • Aravani D.
        • Kassi E.
        • Chatzigeorgiou A.
        • Vakrou S.
        Cardiometabolic syndrome: an update on available mouse models.
        Thromb Haemostasis. 2021; 121: 703-715
        • Lundåsen T.
        • Liao W.
        • Angelin B.
        • Rudling M.
        Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (Cyp7a1) in leptin-deficient (ob/ob) mice.
        J Biol Chem. 2003; 278: 43224-43228
        • Silver D.L.
        • Jiang X.C.
        • Arai T.
        • Bruce C.
        • Tall A.R.
        Receptors and lipid transfer proteins in HDL metabolism.
        Ann NY Acad Sci. 2000; 902 (;discussion 111–102): 103-111
        • Huang Z.Y.
        • Stabler T.
        • Pei F.X.
        • Kraus V.B.
        Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation.
        Osteoarthr Cartil. 2016; 24: 1769-1775
        • Loeser R.F.
        • Arbeeva L.
        • Kelley K.
        • Fodor A.A.
        • Sun S.
        • Ulici V.
        • et al.
        Association of increased serum lipopolysaccharide, but not microbial dysbiosis, with obesity-related osteoarthritis.
        Arthritis Rheumatol. 2022; 74: 227-236
        • Määttä A.M.
        • Salminen A.
        • Pietiäinen M.
        • Leskelä J.
        • Palviainen T.
        • Sattler W.
        • et al.
        Endotoxemia is associated with an adverse metabolic profile.
        Innate Immun. 2021; 27: 3-14
        • Yao Z.
        • Mates J.M.
        • Cheplowitz A.M.
        • Hammer L.P.
        • Maiseyeu A.
        • Phillips G.S.
        • et al.
        Blood-borne lipopolysaccharide is rapidly eliminated by liver sinusoidal endothelial cells via high-density lipoprotein.
        J Immunol. 2016; 197: 2390-2399
        • Huang Z.
        • Kraus V.B.
        Does lipopolysaccharide-mediated inflammation have a role in OA?.
        Nat Rev Rheumatol. 2016; 12: 123-129
        • Choi W.S.
        • Lee G.
        • Song W.H.
        • Koh J.T.
        • Yang J.
        • Kwak J.S.
        • et al.
        The CH25H-CYP7B1-RORα axis of cholesterol metabolism regulates osteoarthritis.
        Nature. 2019; 566: 254-258
        • Tsezou A.
        • Iliopoulos D.
        • Malizos K.N.
        • Simopoulou T.
        Impaired expression of genes regulating cholesterol efflux in human osteoarthritic chondrocytes.
        J Orthop Res. 2010; 28: 1033-1039
        • Du X.M.
        • Kim M.J.
        • Hou L.
        • Le Goff W.
        • Chapman M.J.
        • Van Eck M.
        • et al.
        HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export.
        Circ Res. 2015; 116: 1133-1142