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Trimming the fat — is leptin crosstalk the link between obesity and osteoarthritis?

Published:October 20, 2022DOI:https://doi.org/10.1016/j.joca.2022.10.011
      Historically, the role of obesity in osteoarthritis (OA) has been dismissed as a consequence of excessive mechanical loading. With improved understanding of obesity and metabolic syndrome, cytokines and adipokines (e.g., interleukin (IL)-1, tumor necrosis factor-α (TNF-α), IL-6, leptin) have been demonstrated to play a role in OA, leading to many comprehensive studies on this topic
      • Griffin T.M.
      • Huebner J.L.
      • Kraus V.B.
      • Guilak F.
      Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis.
      • Griffin T.M.
      • Huebner J.L.
      • Kraus V.B.
      • Yan Z.
      • Guilak F.
      Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise.
      • Griffin T.M.
      • Fermor B.
      • Huebner J.L.
      • Kraus V.B.
      • Rodriguiz R.M.
      • Wetsel W.C.
      • et al.
      Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice.
      • 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.
      • Collins K.H.
      • MacDonald G.Z.
      • Hart D.A.
      • Seerattan R.A.
      • Rios J.L.
      • Reimer R.A.
      • et al.
      Impact of age on host responses to diet-induced obesity: development of joint damage and metabolic set points.
      • Harasymowicz N.S.
      • Choi Y.R.
      • Wu C.L.
      • Iannucci L.
      • Tang R.
      • Guilak F.
      Intergenerational transmission of diet-induced obesity, metabolic imbalance, and osteoarthritis in mice.
      • Collins K.H.
      • Sharif B.
      • Reimer R.A.
      • Sanmartin C.
      • Herzog W.
      • Chin R.
      • et al.
      Association of metabolic markers with self-reported osteoarthritis among middle-aged BMI-defined non-obese individuals: a cross-sectional study.
      • Collins K.H.
      • Hart D.A.
      • Seerattan R.A.
      • Reimer R.A.
      • Herzog W.
      High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model.
      • Collins K.H.
      • Herzog W.
      • MacDonald G.Z.
      • Reimer R.A.
      • Rios J.L.
      • Smith I.C.
      • et al.
      Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity.
      • Schott E.M.
      • Farnsworth C.W.
      • Grier A.
      • Lillis J.A.
      • Soniwala S.
      • Dadourian G.H.
      • et al.
      Targeting the gut microbiome to treat the osteoarthritis of obesity.
      • Wu C.L.
      • McNeill J.
      • Goon K.
      • Little D.
      • Kimmerling K.
      • Huebner J.
      • et al.
      Conditional macrophage depletion increases inflammation and does not inhibit the development of osteoarthritis in obese macrophage Fas-induced apoptosis-transgenic mice.
      • Wu C.L.
      • Kimmerling K.A.
      • Little D.
      • Guilak F.
      Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair.
      • Barboza E.
      • Hudson J.
      • Chang W.P.
      • Kovats S.
      • Towner R.A.
      • Silasi-Mansat R.
      • et al.
      Pro-fibrotic infrapatellar fat pad remodeling without M1-macrophage polarization precedes knee osteoarthritis in diet-induced obese mice.
      • Harasymowicz N.S.
      • Clement N.D.
      • Azfer A.
      • Burnett R.
      • Salter D.M.
      • Simpson A.
      Regional differences between perisynovial and infrapatellar adipose tissue depots and their response to class II and class III obesity in patients with osteoarthritis.
      • Collins K.H.
      • Hart D.A.
      • Reimer R.A.
      • Seerattan R.A.
      • Herzog W.
      Response to diet-induced obesity produces time-dependent induction and progression of metabolic osteoarthritis in rat knees.
      • Hamada D.
      • Maynard R.
      • Schott E.
      • Drinkwater C.J.
      • Ketz J.P.
      • Kates S.L.
      • et al.
      Suppressive effects of insulin on tumor necrosis factor-dependent early osteoarthritic changes associated with obesity and type 2 diabetes mellitus.
      • Collins K.H.
      • Paul H.A.
      • Reimer R.A.
      • Seerattan R.A.
      • Hart D.A.
      • Herzog W.
      Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model.
      • Collins K.H.
      • Reimer R.A.
      • Seerattan R.A.
      • Leonard T.R.
      • Herzog W.
      Using diet-induced obesity to understand a metabolic subtype of osteoarthritis in rats.
      • Messier S.P.
      • Mihalko S.L.
      • Legault C.
      • Miller G.D.
      • Nicklas B.J.
      • DeVita P.
      • et al.
      Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial.
      • Somers T.J.
      • Blumenthal J.A.
      • Guilak F.
      • Kraus V.B.
      • Schmitt D.O.
      • Babyak M.A.
      • et al.
      Pain coping skills training and lifestyle behavioral weight management in patients with knee osteoarthritis: a randomized controlled study.
      • Collins K.H.
      • Schwartz D.J.
      • Lenz K.L.
      • Harris C.A.
      • Guilak F.
      Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury.
      . We wish to clarify some of the points raised and discuss our perspective on the complex mechanisms of leptin in OA.

      Keywords

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