Increased synovial lipodystrophy induced by high fat diet aggravates synovitis in experimental osteoarthritis

Abstract

BackgroundMetabolic syndrome (MetS) may be associated with knee osteoarthritis (OA), but the association between the individual components and OA are not well-understood. We aimed to study the effect of hypercholesterolemia on synovial inflammation in knee OA.MethodsOA was surgically induced in rabbits fed with standard diet (OA group, n = 10) or in rabbits fed with high fat diet (OA-HFD, n = 10). Healthy rabbits receiving standard diet (Control, n = 10) or fed with HFD (HFD, n = 6) were also monitored. Twelve weeks after OA induction, synovial membranes were isolated and processed for studies.ResultsAnimals fed HFD showed higher levels of total serum cholesterol, triglycerides and C-reactive protein than control rabbits. Twelve weeks after OA induction, synovial membrane inflammation and macrophage infiltration were increased in rabbits with OA, particularly in the OA-HFD group. Extensive decrease of synovial adipose tissue area, adipocyte size and perilipin-1A synthesis were observed in the OA-HFD group in comparison to the OA and control groups. The HFD further increased the proinflammatory mediators IL-1β, IL-6 and TNF in the OA synovium. However, the synovial gene expression of adipokines, such as leptin and adiponectin, were markedly decreased in the rabbits with OA, especially in the OA-HFD group, in correlation with adipose tissue loss. However, circulating leptin was upregulated in the HFD and OA-HFD groups.ConclusionOur results indicate that a HFD is an aggravating factor worsening synovial membrane inflammation during OA, guided by increased infiltration of macrophages and removal of the adipose tissue, together with a remarkable presence of proinflammatory factors. Synovial adipocytes and dyslipemia could probably play pivotal roles in OA joint deterioration in patients with MetS, supporting that the link between obesity and OA transcends mechanical loading.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1473-z) contains supplementary material, which is available to authorized users.

Systemic and local adipose tissue in knee osteoarthritis

“…These suggested that leptin was necessary in the development and progression of obesity-related OA. In contrast, a recent study reported inconsistent findings showing that leptin gene expression was markedly decreased in the synovial membrane in the rabbits with OA 62 . Adipose tissue may affect the metabolism of joint tissues through secretion of adipokines, leading to the pathological changes in knee OA.…”

Purinergic System Signaling in Metainflammation-Associated Osteoarthritis

“…This highlights the importance of M1 macrophage subsets in the development of obesity-associated OA ( 57 ). Furthermore, HFD aggravates synovial inflammation during OA, by increasing macrophage infiltration and metabolic-mediated remodeling of adipose tissue, together with a significant presence of pro-inflammatory factors ( 58 ). Additionally, free fatty acids induce activation of Toll-like receptor 2 (TLR2) or TLR4, trigger macrophage recruitment, and activate the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome ( 59 ).…”

Modulation of the Inflammatory Process by Hypercholesterolemia in Osteoarthritis

“…Rabbits were kept in individual transparent 50 × 40 × 40 cm cages that allow social interactions. After 2 weeks of acclimatization with ad-libitum access to water and standard commercial chow, rabbits were randomly separated into four groups (20).…”

“…Since rabbits have been claimed as the best animal model for lipid-related research (17,18), we employed rabbits with normal cholesterol metabolism in our study, in order to analyse the effect of high fat diet (HFD) on OA progression. Furthermore, we carried out an experimental model of high lipid intake that is not associated to an increase in weight gain, that allows to adequately address the contribution of added mechanical load and hyperlipidaemia in cartilage alterations (19)(20)(21).…”