A new study of how the different saturated fats produce different illnesses
Saturated fatty acids induce development of both metabolic syndrome and osteoarthritis in rats
The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA, C12:0) from coconut and palm oil, myristic acid (MA, C14:0) mainly from palm kernel oil, coconut oil, and butter fat, palmitic acid (PA, C16:0) naturally present in butter, cheese, milk, and meat , as well as cocoa butter, soybean oil, and sunflower oil and stearic acid (SA, C18:0) abundant in animal fat (up to 30%) , cocoa butter and shea butter.
The aim of this study was to investigate whether diets containing individual SFA together with excess simple carbohydrates induce osteoarthritis (OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats were given either a corn starch diet or a diet composed of simple carbohydrates together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also exhibited cartilage degradation and subchondral bone changes similar to OA.
In contrast, replacement of beef tallow with LA decreased signs of metabolic syndrome together with decreased cartilage degradation. Furthermore, PA and SA but not LA increased release of matrix sulphated proteoglycans in cultures of bovine cartilage explants or human chondrocytes. In conclusion, we have shown that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like knee changes. Thus, diets containing SFA are strongly relevant to the development or prevention of both OA and metabolic syndrome.
This study illustrates the reason why we advocate for the use of extra virgin olive oil which is rich in unsaturated fats since all of the saturated fats have negative though different consequences.
The worldwide incidence of obesity has doubled since 1980, now affecting 475–600 million people, depending on the BMI cut-off used in the estimates16. The incidence of OA has also markedly increased over a similar time period17, leading to well-documented support for the concept that obesity is a modifiable risk factor for the incidence and progression of OA18. The prevalence of both obesity and OA are greatest in patients over 65 years of age, and this is an increasing segment of the world’s population. Since both obesity and OA reduce mobility and increase cardiovascular risk, weight loss and exercise are recognised as key components for treatment of obese patients with OA18. Thus, understanding the common mediators for obesity and OA is clearly relevant to provide realistic and sustainable treatment options for obesity-associated OA.
Increased intake of dietary fat is one of the most important factors linking obesity and OA. Dietary fat is a key contributor to obesity and may help uncover the complex relationships between obesity and OA19. In obesity-related OA, SFA are relevant as they are the major dietary fatty acids. Our study strongly indicates that SFA produce parallel changes over the same time-frame in metabolic syndrome and typical OA-like lesions in the knee joint combined with increased chondrocyte death and breakdown of matrix in isolated bovine and human chondrocytes. Overall, the changes increase with SFA chain length with minimal changes following LA treatment to marked changes with SA treatment. These changes may be further increased by the presence of trans fatty acids as in beef tallow, but this proposal needs to be further tested by treatment with pure trans fatty acids. A plausible mechanism is suggested by the correlation between obesity and OA-like changes and plasma leptin concentrations but other hormones and cytokines released from macrophages may also be involved, as discussed below. This is consistent with the reported increase in palmitate- or stearic acid-induced apoptosis in chondrocytes10,20. In addition, previous studies have reported that SFA-rich high-fat diet increased the severity of OA8,21,22.
The changes in cartilage observed in this study are characteristic of OA-induced cartilage damage with increased PA and SA inducing marked depletion of proteoglycan content and increased expression of MMP13 and COL10 proteins shifting the balance of matrix homeostasis towards catabolism. MMPs are capable of degrading all components of the extracellular matrix, and their enhanced activity has been strongly implicated in cartilage degeneration23. Hypertrophy is known to trigger apoptosis of cartilage cells. The type of fatty acid clearly plays a role since LA did not induce these changes. PA and SA showed decreased proteoglycan content and increased release of sGAG, which confirmed their destructive properties on both cartilage explants and re-differentiated chondrocyte pellets. We further studied the effects of SFA and inflammatory cytokines such as IL-1β on chondrocytes. Co-treatment with IL-1β decreased the proteoglycan content and facilitated the increased release of sGAG in both human and bovine cartilage. Increases in gene expression of MMP13, ADAMTS 4 and 5 in PA- and SA-treated cartilage explants correlated with the increased release of sGAG. These results collectively suggest that catabolic effects of PA and SA together with IL-1β co-treatment in both human and bovine cartilage are likely to be mediated by the increased expression of cartilage-degrading enzymes that then trigger the changes similar to OA in chondrocytes. Furthermore, the number of empty lacunae is a clear indicator of osteocyte death24. In our recent study, the functional properties of osteocytes changed in OA patients, signifying the potential role of these cells in subchondral bone sclerosis25. Our results confirmed the increased presence of empty lacunae in H, HPA and HSA diet rats suggesting increased bone remodelling and unregulated mineral metabolism.
The correlation between obesity and OA is well-established, indicating that metabolic-induced inflammation in obesity26 plays an important role in OA27. The initiators of the inflammatory processes in rats fed this obesogenic diet are most likely to be SFA, since SFA such as PA activate macrophages10, and therefore increase infiltration of inflammatory cells throughout the body. Thus, obesity by itself does not cause OA, nor the reverse, but increased circulating SFA may induce infiltration of inflammatory cells throughout the body to produce parallel development of both disease states. While SFA may initiate the inflammation, there is good evidence that adipokines produced by inflammatory cells within fat pads also produce major physiological responses and may therefore increase the inflammatory responses in OA28. Key cytokines are likely to include leptin and adiponectin, with possible roles of more recently discovered adipokines such as resistin and visfatin, in both obesity and OA4,28,29. The involvement of these cytokines in the development of obesity-induced OA could underlie the improvements following loss of abdominal obesity30, and so decreased cytokine production, such as improved lean mass/fat mass ratio leading to increased mobility and physical activity with decreased OA-induced pain, for example in the knees. The local inflammatory reactions in obesity-associated OA may then be increased by the development of insulin resistance in type 2 diabetes31. Type 2 diabetes is strongly predictive of the severity of OA, independent of BMI and age32,33, suggesting the involvement of insulin as type 2 diabetes is an insulin-resistant state. Insulin decreased autophagy in immortalised human chondrocytes and human cartilage explants, providing a mechanism by which cartilage could be damaged in an insulin-resistant state34. The correlation of decreased plasma insulin concentrations and decreased OA-like changes in rats fed LA, and the increased OA-like changes in rats fed PA and SA in our study strongly supports the role of insulin in OA associated with glucose intolerance and obesity. Oxidative stress as an increased biological activity of oxygen free radicals is also a key initiator of damage in both obesity35 and OA36. Ageing is associated with an increased oxidative stress, and also increased prevalence of both obesity and OA, suggesting oxidative stress as a possible causative link. Further, functional foods such as omega-3 polyunsaturated fatty acids may improve oxidative status as an important therapeutic mechanism37.
The limitations of this study include that we have not measured the morphological changes of the synovium or changes in synovial fluid cytokine concentrations. These two additional parameters may contribute additional insights to understanding local changes due to inflammation in SFA diets and so improve understanding of obesity-induced OA.
In conclusion, this study provides evidence that SFA can produce similar changes in both metabolic syndrome and OA. These changes correlate with the plasma concentrations of leptin and insulin, both involved in obesity, type 2 diabetes and OA. Our data suggest that replacement of traditional diets containing coconut-derived LA with palm oil-derived PA or animal fat-derived SA has the potential to worsen the development of both metabolic syndrome and OA. Further, human clinical trials are necessary to determine whether replacement of PA and SA in the diet with LA will attenuate or reverse the development of both OA and metabolic syndrome, especially obesity and hypertension.