Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats

We previously reported that renal injury in hyperlipidemic, obese Zucker rats was associated with a relative deficiency of tissue polyunsaturated fatty acids (PUFA). In the present study 10-week-old obese Zucker rats were pair fed regular chow or chow containing either 20% sunflower oil rich in n-6 PUFA, fish oil rich in n-3 PUFA, coconut oil medium-chain saturated fatty acid, or beef tallow long-chain saturated fatty acid. At 34 weeks of age there were comparable reductions in albuminuria, mesangial matrix expansion, and glomerulosclerosis in the fish oil and sunflower oil groups. While both fish oil and sunflower oil reduced serum triglycerides, and improved the composition of triglyceride-enriched lipoproteins, only fish oil decreased serum cholesterol. The effect of the dietary fatty acid supplementation on fatty acid profiles were similar in isolated glomeruli and cortical tissue. In general, the amelioration in injury in the fish oil and sunflower oil fed rats was most closely linked to glomerular levels of PUFA, either n-6 or n-3. These data suggest that hyperlipidemia and abnormalities in tissue FA are closely linked, and that dietary supplementation with PUFA may ameliorate chronic, progressive renal injury.     

Chemokines and chemokine receptors are involved in the resolution or progression of renal disease

Locally secreted chemokines mediate leukocyte recruitment during the initiation and amplification phase of renal inflammation. In turn, the infiltrating leukocytes contribute to renal damage by releasing inflammatory and profibrotic factors. Rapid down modulation of the chemokine signal will support resolution of acute inflammation, whereas progression occurs if ongoing or repeated renal injury maintains continuous local chemokine secretion and leukocyte influx into the glomerulus or the interstitial space. In glomerular injury proteinuria itself as well as glomerular secreted cytokines stimulate downstream tubular epithelial cells to also secrete chemokines. During primary tubular injury, tubular epithelial cells directly become a major site of chemokine production. This in turn supports leukocyte infiltration and activation. Infiltrating leukocytes stimulate fibroblast proliferation and matrix synthesis, leading to widening of the interstitial space. The specific and intricate renal vascular architecture renders the organ susceptible to ischemic damage as interstitial volume increases. Ischemia in turn serves as a stimulus for chemokine and cytokine production and matrix synthesis. The mutual stimulation between fibroblasts and infiltrating leukocytes supports progressive tubular damage, renal fibrosis, and glomerulosclerosis. Potentially this vicious circle leading to progression of chronic nephropathies offers the opportunity for therapeutic intervention. Interfering with the chemokine network that mediates leukocyte recruitment may represent a promising therapeutic option for progressive renal disorders and renal fibrosis. This article summarizes the present data on the role of chemokines in acute and chronic renal disease with special emphasis on their potential role in mediating resolution or progression of renal disease as well as on therapeutic options.     

Plasma and erythrocyte phospholipid fatty acids composition in Serbian hemodialyzed patients

Dyslipidemia is one of the possible risk factors for advanced atherosclerosis in patients with chronic renal failure. Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in patients with renal failure. The aim of this study was to determine specific characteristics of plasma and erythrocyte phospholipid content and fatty acid composition in 37 patients with chronic renal failure on hemodialysis (HD). The results were compared with the characteristics of healthy subjects. Briefly, plasma triglyceride (p < 0.001), total cholesterol (p < 0.05), and total phospholipids (p < 0.01) levels were significantly higher and HDL-cholesterol level significantly lower (p < 0.01) in HD patients. Plasma phosphatidylcholine and phosphatidylethanolamine concentration were significantly higher (p < 0.001) in HD patients. The plasma phospholipid fatty acids composition indicated significantly (p < 0.01) higher level of oleic (18:1 n-9) and lower levels of eicopentaenoic (20:5 n-3 EPA) and docosahexaenoic (22:6 n-3 DHA) acids (p < 0.05). However, in HD patients, the relative concentration of plasma phospholipid n-6 polyunsaturated fatty acid (PUFA) was significantly lower (p < 0.05). The fatty acid composition of erythrocyte phospholipid in HD patients was modified with EPA and DHA levels significantly lowered (p < 0.05). Our results demonstrate an abnormal phospholipid metabolism and deficiency of n-3 PUFA in plasma and erythrocyte phospholipids in hemodialyzed patients.     

The role of fish oil/omega-3 fatty acids in the treatment of IgA nephropathy

Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported in recent epidemiologic studies and randomized clinical trials in a variety of cardiovascular and autoimmune diseases. Fish and marine oils are the most abundant and convenient sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major n-3 fatty acids that serve as substrates for cyclooxygenase and lipoxygenase pathways leading to less potent inflammatory mediators than those produced through the n-6 PUFA substrate, arachidonic acid. N-3 PUFA can also suppress inflammatory and/or immunologic responses through eicosanoid-independent mechanisms. Although the pathophysiology of IgA nephropathy is incompletely understood, it is likely that n-3 PUFA prevents renal disease progression by interfering with a number of effector pathways triggered by mesangial immune-complex deposition. In addition, potential targets of n-3 PUFA relevant to renal disease progression could be similar to those involved in preventing the development and progression of cardiovascular disease by lowering blood pressure, reducing serum lipid levels, decreasing vascular resistance, or preventing thrombosis. In IgA nephropathy, efficacy of n-3 PUFA contained in fish oil supplements has been tested with varying results. The largest randomized clinical trial performed by our collaborative group provided strong evidence that treatment for 2 years with a daily dose of 1.8 g of EPA and 1.2 g of DHA slowed the progression of renal disease in high-risk patients. These benefits persisted after 6.4 years of follow up. With safety, composition, and dosing convenience in mind, we can recommend two products that are available as pharmaceutical-grade fish-oil concentrates, Omacor (Pronova Biocare, Oslo, Norway) and Coromega (European Reference Botanical Laboratories, Carlsbad, CA).     

Plasma and Erythrocyte Phospholipid Fatty Acids Composition in Serbian Hemodialyzed Patients

Dyslipidemia is one of the possible risk factors for advanced atherosclerosis in patients with chronic renal failure. Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in patients with renal failure. The aim of this study was to determine specific characteristics of plasma and erythrocyte phospholipid content and fatty acid composition in 37 patients with chronic renal failure on hemodialysis (HD). The results were compared with the characteristics of healthy subjects. Briefly, plasma triglyceride (p < 0.001), total cholesterol (p < 0.05), and total phospholipids (p < 0.01) levels were significantly higher and HDL-cholesterol level significantly lower (p < 0.01) in HD patients. Plasma phosphatidylcholine and phosphatidylethanolamine concentration were significantly higher (p < 0.001) in HD patients. The plasma phospholipid fatty acids composition indicated significantly (p < 0.01) higher level of oleic (18:1 n-9) and lower levels of eicopentaenoic (20:5 n-3 EPA) and docosahexaenoic (22:6 n-3 DHA) acids (p < 0.05). However, in HD patients, the relative concentration of plasma phospholipid n-6 polyunsaturated fatty acid (PUFA) was significantly lower (p < 0.05). The fatty acid composition of erythrocyte phospholipid in HD patients was modified with EPA and DHA levels significantly lowered (p < 0.05). Our results demonstrate an abnormal phospholipid metabolism and deficiency of n‐3 PUFA in plasma and erythrocyte phospholipids in hemodialyzed patients.     

Relationship between plasma phospholipid polyunsaturated fatty acid composition and bone disease in renal transplantation

To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.     

Dietary intake of polyunsaturated fatty acids and risk of hip fracture in men and women

Summary

Data on the impact of polyunsaturated fatty acid intake on hip fracture risk are inconsistent. We investigated this association in 75,878 women and 46,476 men and did not find a significant role for polyunsaturated fatty acid intake in the prevention of hip fractures.

Introduction

Polyunsaturated fatty acids (PUFA) are important in the prevention of chronic diseases, but studies of bone health report inconsistent results. Our aim was to investigate the association between dietary PUFA intake and risk of hip fracture in two large prospective cohorts of men and women with long follow-up times and frequently updated dietary data.

Methods

The study population included 75,878 women and 46,476 men free of osteoporosis at baseline. Dietary intakes were assessed by a food frequency questionnaire at baseline and several times during the follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate relative risks (RR).

Results

During 24?years of follow-up, we identified 1,051 hip fracture cases due to low or moderate trauma among the women and 529 cases among the men. In the pooled analyses, no statistically significant associations were found between intakes of total PUFA [RR in the highest vs. lowest quintile: 0.99, 95% confidence interval (CI) 0.69, 1.43; p value for trend is =0.83], total n-3 PUFA (RR 0.89, 95% CI 0.75, 1.06; p value for trend is =0.26), total n-6 PUFA (RR 0.99, 95% CI 0.71, 1.38; p value for trend is =0.82), n-6/n-3 PUFA ratio or individual PUFAs, and hip fracture risk. However, in women low intakes of total PUFA, total n-6 PUFA, and linoleic acid were associated with higher risk.

Conclusions

This study does not support a significant role for PUFA intake in the prevention of hip fractures, although low total PUFA, n-6 PUFA, or linoleic acid intakes may increase the risk in women.     

Stellenwert von langkettigen Omega-3-Fettsäuren bei Prostatakrebs

The benefits of long chain polyunsaturated omega-3 fatty acids (n-3 PUFA) from fish or administered as supplements remain controversial regarding prostate cancer (PCa). Based on the currently available evidence no clear benefit of n-3 PUFA intake to generally reduce PCa incidence has been found. On the other hand n-3 PUFAs have a clear influence on the development of already existing PCa. The intake of n-3-PUFAs considerably reduces the risk of metastasis and PCa-related mortality.     

The effect of n-3 fatty acids on heart rate variability in patients treated with chronic hemodialysis.

OBJECTIVE: The aim of the present study was to address the effect of n-3 polyunsaturated fatty acids (PUFAs) on heart rate variability (HRV) in patients treated with chronic hemodialysis. DESIGN: We performed a randomized, placebo-controlled intervention trial. SETTING: The study took place at two hospital-based dialysis centers. PATIENTS: Thirty patients with documented cardiovascular disease who were treated with hemodialysis for at least 6 months were included. INTERVENTION: Treatment consisted of 1.7 g of n-3 PUFA or a control treatment (olive oil). MAIN OUTCOME MEASURE: The outcome measure was 24-hour Holter recordings with time domain HRV measurements at baseline and after 3 months of treatment. Blood samples were obtained to assess the content of n-3 PUFA in serum phospholipids before and after treatment. RESULTS: n-3 PUFA did not significantly affect time domain parameters of HRV, compared with a control group. CONCLUSION: We conclude that treatment with n-3 PUFA does not increase HRV in patients treated with chronic hemodialysis, a result that may have been compromised by a small sample size.     

The effect of n-3 fatty acids on C-reactive protein levels in patients with chronic renal failure.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic renal failure (CRF). C-reactive protein (CRP), a strong independent risk marker of CVD, is elevated in a large proportion of patients with CRF. The long-chain n-3 polyunsaturated fatty acids (PUFA) have cardioprotective effects, which may be partly attributed to their anti-inflammatory properties. OBJECTIVE: The study objective was to investigate the effect of n-3 PUFA on serum levels of CRP in patients with CRF. DESIGN: We performed a randomized, double-blind, placebo-controlled study. SETTING: The study took place at an outpatients clinic at the Department of Nephrology, Aalborg Hospital, Denmark. PATIENTS: The study comprised 46 patients (30 men and 16 women; mean age 59 +/- 11 years) with a serum creatinine level in the range of 150 to 400 micromol/L. INTERVENTION: The patients were randomly assigned to daily supplementation with 2.4 g n-3 PUFA or identical capsules containing 2.4 g of olive oil (control) for 8 weeks. MAIN OUTCOME MEASURE: CRP was measured with a high-sensitivity C-reactive protein (hs-CRP) assay and the content of n-3 PUFA in granulocyte membranes before and after supplementation. RESULTS: The n-3 PUFA concentration increased in granulocytes after the n-3 PUFA supplements but was unaltered by the control oil. A nonsignificant reduction in hs-CRP was observed in the n-3 PUFA group after supplementation (2.46 vs. 1.47 mg/L; P = .06), and hs-CRP was unaltered by the control oil (3.27 vs. 3.14 mg/L; P = .12). There was no difference in median hs-CRP change in the two groups. CONCLUSION: A trend was seen toward a reduction in hs-CRP in the n-3 PUFA group, but there was no significant difference in hs-CRP levels when both groups were compared.     

Polyunsaturated Fatty Acids in Human Milk and Their Role in Early Infant Development

The lipid fraction of human milk represents themain source of energy for the newborn infant andsupplies essential nutrients such as fat-solublevitamins and polyunsaturated fatty acids(PUFA).³ The essential fatty acids linoleic and-linolenic acids are precursors of long-chainpolyunsaturated fatty acids (LC-PUFA), such asarachidonic (C20:4 n-6) and docosahexaenoic (C22:6 n-3)acids, present in human milk in considerable amounts.LC-PUFA are indispensable structural components of allcellular membranes, and they are incorporated inrelatively large amounts during early growth of the brain and the retina. Moreover, some LC-PUFAare precursors of eicosanoids, molecules with potentbiological activity that modulates various cellular andtissue processes. The supply of long-chain fatty acids has been associated with functionaloutcomes of the recipient infants such as visual acuityand development of cognitive functions during the firstyear of life. Here we discuss the PUFA composition of human milk, factors which determine andmodulate milk PUFA content, and possible effects of milkLC-PUFA on infant growth and development.     

Preoperative short-term parenteral administration of polyunsaturated fatty acids ameliorates intestinal inflammation and postoperative ileus in rodents

Purpose  

Abdominal surgery results in an inflammation of the intestinal muscularis externa (ME), subsequently leading to postoperative ileus (POI). Polyunsaturated fatty acids (PUFA) are known to modulate inflammation. The aim of this study was to analyze the effect of preoperative parenteral administration of marine (n-3) or soybean (n-6) PUFA lipid emulsions (PUFA-LE) on POI and tissue fatty acid profiles.     

Evaluation of fat nutrition in the energy intake on low protein diets for patients with chronic renal failure]

Low protein diet has been proven to retard the progression of chronic renal failure. In this diet, the energy intake depends mainly on fats and carbohydrates instead of protein, and precautions should be taken against increasing risks of both lipid nephrotoxicity and atherosclerosis. In order to assess the adequacy of fat nutrition in a low protein diet for patients with chronic renal failure, we evaluated the total amounts of dietary fat intake, dietary individual fatty acid intake and serum individual fatty acid concentrations in 16 patients, whose mean creatinine clearance was 21.3 +/- 12.1 ml/m, serum creatinine 3.8 +/- 2.2 mg/dl and serum urea nitrogen 41.5 +/- 18.6 mg/dl. The percentage ratio of fat intake to total energy intake was 26.7 +/- 5.2%. The ratio of intake of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids was 1:2:1.8, and n-6/n-3 was 8.5 +/- 9.3. These were significant correlations between dietary intake and the serum concentrations in both EPA and the ratio of EPA/AA. Consequently, it might be considered that polyunsaturated fatty acids intake should be lowered and patients with chronic renal failure on a low protein diet should be advised about the proper selection of foods containing animal protein and plant-derived oil. It may be beneficial to recommend the intake of more EPA and lowering the ratio of n-6/n-3 intake might be useful in improving the fat nutrition to adequate levels in these patients.     

Marine n-3 Polyunsaturated Fatty Acid Supplementation and Quality of Life After Kidney Transplant

Marine n-3 polyunsaturated fatty acids (PUFAs) may improve cardiovascular, renal, and mental health. No previous trial has investigated the effects of marine n-3 PUFA supplementation on quality of life (QoL) indices after renal transplant.

Transgenic Restoration of Long-Chain n-3 Fatty Acids in Insulin Target Tissues Improves Resolution Capacity and Alleviates Obesity-Linked Inflammation and Insulin Resistance in High-Fat�CFed Mice

OBJECTIVE

The catabasis of inflammation is an active process directed by n-3 derived pro-resolving lipid mediators. We aimed to determine whether high-fat (HF) diet-induced n-3 deficiency compromises the resolution capacity of obese mice and thereby contributes to obesity-linked inflammation and insulin resistance.

RESEARCH DESIGN AND METHODS

We used transgenic expression of the fat-1 n-3 fatty acid desaturase from C. elegans to endogenously restore n-3 fatty acids in HF-fed mice. After 8 weeks on HF or chow diets, wild-type and fat-1 transgenic mice were subjected to insulin and glucose tolerance tests and a resolution assay was performed. Metabolic tissues were then harvested for biochemical analyses.

RESULTS

We report that the n-3 docosanoid resolution mediator protectin D1 is lacking in muscle and adipose tissue of HF-fed wild-type mice. Accordingly, HF-fed wild-type mice have an impaired capacity to resolve an acute inflammatory response and display elevated adipose macrophage accrual and chemokine/cytokine expression. This is associated with insulin resistance and higher activation of iNOS and JNK in muscle and liver. These defects are reversed in HF-fed fat-1 mice, in which the biosynthesis of this important n-3 docosanoid resolution mediator is improved. Importantly, transgenic restoration of n-3 fatty acids prevented obesity-linked inflammation and insulin resistance in HF-fed mice without altering food intake, weight gain, or adiposity.

CONCLUSIONS

We conclude that inefficient biosynthesis of n-3 resolution mediators in muscle and adipose tissue contributes to the maintenance of chronic inflammation in obesity and that these novel lipids offer exciting potential for the treatment of insulin resistance and diabetes.Obesity is linked to chronic inflammation that plays a key role in the pathogenesis of insulin resistance, leading the way to type 2 diabetes and cardiovascular disease (1,2). Efforts to understand this process have focused on identifying the many factors that may initiate and promote inflammation. We took an alternate approach with the view that pathological inflammation in obesity likely represents an impaired endogenous capacity to “switch off” or more precisely counterregulate the natural immune response to adipose tissue expansion and lipid excess.The newly identified genus of n-3 derived lipid mediators termed resolvins and protectins have been shown to play an important role in the endogenous regulation of inflammation (3,4). Interestingly, dietary long-chain n-3 polyunsaturated fatty acid (PUFA) insufficiency has been linked to the incidence of chronic metabolic disorders, including type 2 diabetes and cardiovascular disease (5–7). It is thus conceivable that inefficient biosynthesis of n-3 resolution mediators due to low substrate availability might inherently contribute to the development of obesity-linked inflammation.González-Périz et al. recently showed that acute administration of n-3 derived Resolvin E1 (RvE1) prevents hepatic steatosis in genetically obese mice (8). However, the other main resolution mediator Protectin D1 (PD1) remains to be investigated, and it is unknown whether high-fat (HF) feeding per se actually restricts resolution mediator biosynthesis and whether this might alter the endogenous resolution capacity of obese mice. Furthermore, it is critical to determine whether n-3 lipid mediators regulate key obesity-related inflammatory reactions such as macrophage accrual in adipose tissue or activation of inflammatory signaling molecules such as JNK and iNOS that play a role in the etiology of insulin resistance (1,2).Unfortunately, studying the effects of dietary n-3 content in the context of HF feeding has proven to be rather complicated because incorporation of n-3 fatty acids in rodent diets often prevents weight gain (9). As a result, it is not clear whether it is the lack of weight gain or the n-3 fatty acids themselves that offer the protection from insulin resistance and type 2 diabetes and what mechanism underlies this protection. Therefore, innovative models that overcome the requirement for dietary manipulation are needed to help clarify whether or not n-3 fatty acids act directly to prevent obesity-linked insulin resistance and which mechanisms are involved.The fat-1 transgenic mouse has been genetically engineered to ubiquitously express the fat-1 n-3 fatty acid desaturase from C. elegans (10). This enzyme, not found in mammals, efficiently converts endogenous n-6 to n-3 fatty acids such that, in fat-1 mice fed a diet extremely rich in n-6 and deficient in n-3, the tissue n-6:n-3 ratio is ∼1:1 compared with ∼50:1 in wild-type animals. The fat-1 transgenic mouse therefore represents the ideal model to study the effects of n-3 fatty acids in an environment that is not confronted by dietary issues.Herein we show that HF feeding wild-type mice results in diminished n-3 docosanoid resolution mediator synthesis in muscle and adipose tissue and impaired resolution. Transgenic restoration of n-3 fatty acids in HF-fed fat-1 mice improved resolution capacity and prevented the development of obesity-linked inflammation and insulin resistance. These data uncover a new role for pro-resolving lipid mediators in the counterregulation of obesity-linked inflammation and its associated metabolic complications.     

n-3 Fatty acids and their role in nephrologic practice

During the past year, a newly reported clinical trial has strengthened the argument for recommending daily treatment with n-3 polyunsaturated fatty acids in patients with immunoglobulin A nephropathy (the most common form of primary glomerulonephritis in the world) who are at high risk for progression of renal disease. Studies are underway that involve a combination of cyclosporine A, a commonly prescribed immunosuppressive agent in solid-organ transplantation, with a high-potency n-3 polyunsaturated fatty acid to reduce cyclosporine toxicity. Two studies reported during the past year show promise that dietary supplementation with n-3 polyunsaturated fatty acids will substantially decrease vascular access graft thrombosis in patients receiving maintenance hemodialysis, and may reduce hypercalciuria in patients who suffer from kidney stones.     

n-3多不饱和脂肪酸对人结肠癌细胞增殖与凋亡的影响

目的探讨n-3多不饱和脂肪酸（n-3PUFA）对人结肠癌细胞HT．29的作用及其机制。方法应用MTT比色法、细胞的形态学观察（Hochest33258染色）、DNA凝胶电泳、流式细胞技术检测二十二碳六烯酸（DHA）对HT．29增殖和凋亡的影响：气相色谱分析的方法检测DHA对HT-29细胞n-3PUFA和n．6PUFA含量及n-6／n-3PUFA比例的影响。结果DHA在体外对HT．29有明显的增殖抑制作用,10、20、40和80mg儿DHA作用24h时的细胞增殖抑制率分别为16．8％、24．7％、50．0％和60．1％。40mg／LDHA作用24、48和72h的细胞增殖抑制率分别为50．0％、69．9％和77．0％：呈现明显的剂量和时间效应关系。荧光染色可观察到细胞核染色质浓集,核浓缩核碎裂．并出现典型的凋亡小体：DNA凝胶电泳呈现特征性的梯形条带（DNALadder）：流式细胞仪检测显示经DHA处理后HT-29DNA合成前期（G,期）细胞比例较对照组增加（72．1％比51．3％）,DNA合成期（S期）细胞比例明显减少（19．9％比38．9％）,细胞呈现明显的G,期阻滞;气相色谱分析显示．DHA可以降低HT-29细胞内n-6PUFA而提高n-3PUFA含量,降低n-6／n-3PUFA比率。结论n-3PUFA通过抑制细胞增殖和诱导细胞凋亡来阻遏结肠癌细胞的生长．这种作用的机制可能为降低了细胞的n-6／n-3PUFA的比例。     

Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study

In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST). MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-CE MRI, read for cartilage morphology according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI. 472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosahexaenoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis. In conclusion, systemic levels of n-3 and n-6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.     

Marine n-3 PUFA protects hearts from I/R injury via restoration of mitochondrial function

Abstract

Objectives. Overwhelming evidence shows that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) elicits protective effects on patients with cardiovascular disease. However, the detailed mechanisms underlying n-3 PUFA-mediated cardioprotection are unknown, and examined in the present study. Methods: We evaluated heart performances with Langendorff perfusion apparatus. Meanwhile, whole mitochondria were purified from non-perfused hearts for functional assessment, and lipid peroxidation level was measured as well. Results. Compared with control groups, hearts from n-3 PUFA-supplemented rats showed improved functional recovery and reduced tissue injury following ischemia/reperfusion (I/R). Furthermore, the mitochondrial function of PUFA-treated hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity. In addition, thiobarbituric acid-reactive substance or TBARS assay revealed that lipid peroxidation product, malondialdehyde or MDA, in the mitochondria was significantly reduced by PUFA treatment. Conclusion. Taken together, our data indicate that marine n-3 PUFA could improve cardiac performance after I/R injury by restoring mitochondrial respiratory activities and attenuating lipid peroxidation.     

TGF-β/Smad Signaling in Kidney Disease

Chronic progressive kidney diseases typically are characterized by active renal fibrosis and inflammation. Transforming growth factor-β1 (TGF-β1) is a key mediator in the development of renal fibrosis and inflammation. TGF-β1 exerts its biological effects by activating Smad2 and Smad3, which is regulated negatively by an inhibitory Smad7. In the context of fibrosis, although Smad3 is pathogenic, Smad2 and Smad7 are protective. Under disease conditions, Smads also interact with other signaling pathways, such as the mitogen-activated protein kinase and nuclear factor-κB pathways. In contrast to the pathogenic role of active TGF-β1, latent TGF-β1 plays a protective role in renal fibrosis and inflammation. Furthermore, recent studies have shown that TGF-β/Smad signaling plays a regulating role in microRNA-mediated renal injury. Thus, targeting TGF-β signaling by gene transfer of either Smad7 or microRNAs into diseased kidneys has been shown to retard progressive renal injury in a number of experimental models. In conclusion, TGF-β/Smad signaling plays a critical role in renal fibrosis and inflammation. Advances in understanding of the mechanisms of TGF-β/Smad signaling in renal fibrosis and inflammation during chronic kidney diseases should provide a better therapeutic strategy to combat kidney diseases.