Obesity and osteoarthritis: Is leptin the link?

Abstract

There is significant interest in the correlation between adipose regulators of metabolism, inflammation, and the occurrence of osteoarthritis (OA). In this issue of Arthritis & Rheumatism, Griffin and colleagues report the results of their investigation of the role of leptin (1). The investigators hypothesized that obesity in mice resulting from deletion of the leptin gene (ob/ob) or deletion of the leptin receptor gene (db/db) would result in an increased incidence of knee OA, systemic inflammation, and altered subchondral bone morphology. In both of these mouse strains, adiposity was increased by ϳ10-fold compared with controls. Surprisingly, the incidence of OA was not higher in ob/ob and db/db mice than in the control background strain, C57BL/6J mice.These results suggest that obesity alone does not cause OA. However, other changes occurred in these mice due to the loss of leptin function. Leptin-deficient mice had reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis, as previously reported (for review, see ref.2). An extensive analysis of inflammatory molecules was carried out by Luminex bead assay, which revealed an increased level of only interleukin-8 (IL-8) and thus not an overall inflammatory effect of leptin deficiency. These results imply that leptin may be involved in the development of OA. Without leptin, adiposity is insufficient to induce systemic inflammation and knee OA, suggesting a potential role of leptin itself in regulating skeletal and immune functions.

Magnetic Resonance Imaging–Assessed Vastus Medialis Muscle Fat Content and Risk for Knee Osteoarthritis Progression: Relevance From a Clinical Trial

“…These findings may be closely related to adipose tissue metabolism, therefore supporting a potential role of adipokines in knee OA structural progression, as suggested by several studies (36)(37)(38)(39)(40)(41)(42)(43)(44)(45). The greater percentage of TKR in a subgroup of patients was also an interesting finding that merits further exploration.…”

“…However, the finding that an increase in this muscle fat content over time was associated with reduced cartilage volume independent of baseline BMI tempers that hypothesis. Nonetheless, it may be that fatty tissue within the VM may itself produce factors such as adipokines, which in turn might, at least partly, contribute to the worsening of OA symptoms or cartilage degradation (36)(37)(38)(39)(40)(41)(42)(43)(44)(45). In addition, the data showing that in knee OA the quadriceps muscle exhibits atrophy of type 2 fibers (46) could explain the increased fat in the muscle by facilitating fat infiltration.…”

Associations of serum leptin concentration with gender, fat mass, interleukins, and growth factors in patients with osteoarthritis of the knee

“…16 In the present study, the BMI was normal-high, and the serum leptin concentration was correlated with an increase in the total fat mass. The relationship between obesity and OA is an important public health issue.…”

Correlation between serum leptin, cytokines, cartilage degradation and functional impact in obese knee osteoarthritis patients

“…The current study showed a significant correlation between serum leptin and BMI. Revising literature, serum leptin was elevated in obese persons and correlated with the percent of body fat [13,14,22], also leptin concentration decreased after weight loss [22]. High serum and synovial leptin in obese patients with OA were thought to control local inflammatory processes [23].…”