Abstract
High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity.
Highlights
Marrow-derived mesenchymal stem cells and adipose stem cells had altered proliferation and differentiation capacity when cultured with SFA in vitro, providing a potential mechanism for impaired wound healing in obesity[16]
Regardless of the diets and the units used for the FAs, the predominant FA species in serum were palmitic and stearic acid among SFAs, palmitoleic, cis-vaccenic, and oleic acid among monounsaturated fatty acids (MUFAs), linoleic and arachidonic acid among ω-6 PUFAs, docosahexaenoic acid (DHA) among ω-3 PUFAs, and plasmalogen palmitic among plasmalogen derivatives (Fig. 1 and Supplementary Figure 1)
Regardless of the diets and the units used for the FAs, synovial fluid from both non-operated and destabilization of the medial meniscus (DMM) joints had high levels of myristic acid, palmitic acid and stearic acid among SFAs, high levels of palmitoleic acid, cis-vaccenic acid, and oleic acid among MUFAs, high levels of linoleic acid, eicosadienoic acid and arachidonic acid among ω-6 PUFAs, and high levels of α-linolenic acid, eicosapentaenoic acid (EPA) and DHA among ω-3 PUFAs
Summary
Marrow-derived mesenchymal stem cells and adipose stem cells had altered proliferation and differentiation capacity when cultured with SFA in vitro, providing a potential mechanism for impaired wound healing in obesity[16]. Studies suggest that in response to a HF environment, chondrocytes change their metabolic behaviors and increase pro-inflammatory cytokine production[17,18] As they are metabolized, dietary FAs are incorporated into cell membranes, stored in the form of higher-order lipids such as triglycerides and phospholipids, converted into lipid mediators including oxylipins, and/or exist as free form in the serum[19]. Of particular interest are recent findings showing a positive correlation between ear wound healing, knee cartilage regeneration, and protection from OA25 In this regard, the goal of the current study was to examine the relationship between serum and synovial fluid lipidomic panels of FAs with OA severity, joint synovitis and wound regeneration capacity in a previously reported obese animal model of OA in which the mice were fed prescribed HF diets rich in various dietary FAs
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