Effects of dietary fatty acids in an animal model of focal glomerulosclerosis

The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomerulosclerosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer sclerosed glomeruli in the fish oil group (4.0 +/- 0.8% vs. control 19.4 +/- 4.1%, P less than 0.0005 and vs. beef tallow 10.8 +/- 1.9%, P less than 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1 alpha), PGF2 (PGF2 alpha) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production.     

Effect of dietary fish oil on plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha levels in septic rats

Increased mortality from sepsis is associated with high levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha). Linoleic acid, an n-6 essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish oil is rich in n-3 essential fatty acid, the precursor of less active moieties. Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks. The animals then underwent a sham operation or cecal ligation and puncture to induce sepsis. Six hours later, blood was obtained for analysis. The chow and linoleic acid diets produced significant (twofold to fivefold) increases in levels of both TXB2 and PGF1 alpha after sepsis. The essential fatty acid-deficient diet and fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during sepsis. Dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis.     

Fatty acid composition and arachidonic acid concentrations in alveolar bone of rats fed diets with different lipids

Summary The purpose of the present study was to determine if the type of dietary fat can modify the fatty acid composition and arachidonic acid levels in the alveolar bone phospholipids. Three groups of rats were fed nutritionally adequate semipurified diets containing different lipids: 10% corn oil (control, group 1, rich in n-6 fatty acids); 9% butter + 1% corn oil (experimental, group 11, rich in saturated fatty acids); and 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (experimental, group 111, rich in n-3 fatty acids). After 10 weeks of feeding the various diets, rats were killed, maxillae and mandibles were dissected out, and the soft tissue was removed. Bone was frozen in liquid nitrogen and pulverized. Powdered bone was extracted for total lipids, and phospholipids were isolated by column chromatography. The fatty acid composition and arachidonic acid concentrations were determined in total phospholipids after the addition of an internal standard, octadecatetraenoic acid (18: 4n-3), and subsequent gas chromatography. The type of dietary lipids had a profound influence on the fatty acid composition of bone lipids. Arachidonic acid concentrations were significantly lower in total phospholipids of mandibles and maxillae of rats fed the experimental diets than in those fed the control diet. Because arachidonic acid is a precursor of prostaglandin E₂ and leukotriene C₄, a significant reduction in its concentration may result in reduced levels of these eicosanoids in the alveolar bone.Presented in part at the International Association for Dental Research Meeting, Glasgow, Scotland, July 1–4, 1992     

Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism.     

Improvement of Bone Quality in Gonad-Intact Middle-Aged Male Rats by Long-Chain n-3 Polyunsaturated Fatty Acid

The effect of long-chain n-3 polyunsaturated fatty acid (PUFA) on bone measurements was evaluated in gonad-intact middle-aged male rats. Seven rats were killed on day 0 of dietary intervention to determine bone parameters at baseline. Experimental rats (7/group) were fed one of the following lipid treatments (g/kg diet): 167 g safflower oil + 33 g menhaden oil (N6+N3 diet, control), 200 g safflower oil (N6 diet), or 190 menhaden oil + 10 g corn oil (N3 diet). After 20 weeks of dietary treatment, all groups had lower values for peak load and ultimate stiffness in femurs compared to baseline values. Rats fed the N3 diet had the highest values for peak load, ultimate stiffness, and Young’s modulus compared with those fed the N6 and control diets. Compared to baseline, all dietary treatment groups had significantly lower values for trabecular thickness and number in proximal tibia but higher values for trabecular separation and formation rate in proximal tibia and endocortical bone formation rate in tibial shaft. Compared with the control group, rats fed the N3 diet had lower values for formation rate, osteoclast number, and eroded surface in proximal tibia but higher values for periosteal mineral apposition and formation rates in tibia shaft. These findings indicate that a diet rich in long-chain n-3 PUFA mitigate aging-induced loss of bone integrity in intact middle-aged male rats through reducing bone turnover rate by suppressing both bone formation and resorption as a result of a larger net bone volume and modulating endocortical and cancellous bone compartments. Previously presented in part at the 26 th annual meeting of the American Society of Bone and Mineral Research, Seattle, Washington, USA, September 2004, and published in abstract form (Shen CL, Dunn DM, Yeh JK [2005] Dietary fish oil mitigates aging-induced bone loss in middle-aged male rats [abstract]. J Bone Miner Res 19(suppl 1):S205).     

Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model

It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration.     

Dietary fatty acid supplementation modulates the urinary excretion of calcium and oxalate in the rat. Insight into calcium lithogenesis

BACKGROUND: An anomalous plasma phospholipid polyunsaturated fatty acid composition has been reported in calcium nephrolithiasis, and was proposed to play a crucial role in the pathogenesis of hypercalciuria and hyperoxaluria, well-known risk factors for lithogenesis. METHODS: To confirm this hypothesis, we administered rats three different diets rich in coconut, soybean and fish oils, and evaluated their effect on plasma urinary calcium and oxalate excretion, since the quality of fatty acids represents an important factor able to influence the activity of delta-6-desaturase, the rate-limiting enzyme in the biosynthetic pathway of highly unsaturated fatty acids. RESULTS: In comparison with coconut and fish oil, dietary supplementation with soybean oil increased plasma phospholipid arachidonic acid and serum 1,25-vitamin D(3) values, as well as renal tissue calcium content and urinary excretion of sodium, oxalate and calcium. CONCLUSIONS: Our findings demonstrate that the quality of fatty acids may modify the urine excretion of calcium and oxalate, confirming our previous hypothesis of a pathogenetic link between cellular membrane phospholipid polyunsaturated fatty acid composition and calcium nephrolithiasis. In addition, our study provides new insights into the relationship between dietary, environmental factors and renal stone disease.     

Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion

The efficacy of dietary intervention with either 6% protein restriction, fish oil or safflower oil was assessed in the remnant nephron model. Female Munich Wistar rats were prefed for one week prior to 5/6 nephrectomy and followed for the ensuing 28 days. Fish oil, safflower oil and protein restriction prevented the gammaglobulinuria but only fish oil lessened the albuminuria in this model. The remnant nephrons of the fish oil treated rats contained less arachidonic acid and greater quantities of eicosapentaenoic and docosahexaenoic acid than the safflower oil or lab chow fed control rats. The fish oil, and to a lesser extent the safflower oil, treated animals had a higher ratio of 6 keto PGF1 alpha to TX B2 metabolites in their urine. We suggest these changes may be responsible for the lessening in urine protein excretion. Fish oil feeding was more effective than severe protein restriction or safflower oil dietary supplementation in lessening both the gammaglobulinuria and albuminuria of the remnant nephron model.     

Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids

A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.     

Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease.

A paucity of research data exists on the potential for early dietary modification to directly retard cystic growth and proliferation in polycystic kidney disease (PKD). We have therefore examined the relative effects of dietary protein levels and oil type on the progression of disease in a murine model of PKD. In the first study, weanling DBA/2FG-pcy (pcy) mice were fed either a normal (NP), 25%, or low (LP), 6%, casein diet with 10% of either sunflower seed oil (SO) (containing n-6 fatty acids), or fish oil (FO) (containing n-3 fatty acids), in a 2 x 2 design. At the end of the dietary treatment, kidney weight relative to body weight was higher in mice on the NP diets. In addition, kidney phospholipid to kidney weight (mumol/g) was lower in pcy mice on NP diets, indicating that the increased kidney size was largely due to increased cyst development. Replacement of dietary SO with FO resulted in alterations in renal phospholipid fatty acid compositions: 18:2 n-6, 20:4 n-6, and 22:5 n-6 were lower, and 20:5 n-3, 22:5 n-3, and 22:6 n-3 were higher in FO-fed animals. No effect of dietary lipid type on disease progression was noted, however. In a second study, morphometric analysis revealed an 11% lower percentage cyst area and a 46% lower total cyst area (mm2) in kidney sections derived from mice on LP diets compared to NP diets. These results indicate that early dietary protein restriction in PKD prior to clinical manifestation of symptoms of the disease may have a significant impact on the pathogenesis of PKD.     

Dietary Fish Oil Supplementation Adversely Affects Cortical Bone Morphology and Biomechanics in Growing Rabbits

Despite substantial evidence that fish oil-derived (n-3) polyunsaturated fatty acids (PUFA) may protect against cardiovascular disease, the effects of supplements containing (n-3) PUFA on the skeletal system are unknown. Here we investigated how a diet supplemented with 10 g/100 g fish oil affected tibial cortical morphology and mechanical properties in weanling rabbits. Rabbits were subdivided into a normal control (n = 10), a fish oil (n = 20), and a pair-fed (n = 20) group. The pair-fed group was energy restricted to match average body mass of the fish oil group. At completion of the 40 day dietary intervention, control rabbits were significantly heavier than the other two groups. Comparison between control and pair-fed rabbits revealed that energy restriction alone (30%) did not induce significant changes in tibial middiaphyseal morphology, but tibial longitudinal growth was significantly impaired. Most tibial mechanical properties were significantly degraded by energy restriction. Fish oil-supplemented rabbits had significantly smaller middiaphyseal areal properties and shorter tibiae than pair-fed rabbits. Tibial structural properties were significantly reduced in fish oil-fed rabbits, but tibial stress at the proportional limit (material property) was not significantly affected. Our data suggest that 10% fish oil supplementation in the presence of modest vitamin E supplementation can have detrimental effects on the skeleton of rapidly growing rabbits. Received: 11 May 1999 / Accepted: 3 January 2000     

Effects of reduced renal mass on tissue lipids and renal injury in hyperlipidemic rats

Increasing evidence from experimental models of chronic renal failure suggests that abnormalities in lipid metabolism may contribute to progressive renal injury. In the present study, hyperlipidemic obese, and normolipemic lean Zucker rats were subjected to unilateral nephrectomy or sham surgery at eight weeks of age. After 32 weeks, renal injury was greater in obese than in lean rats, and injury was made worse by nephrectomy. Among the major lipid classes, increased renal cortical cholesteryl esters were positively correlated with the degree of renal injury, suggesting that mechanisms analogous to those thought to be important in the pathogenesis of atherosclerosis may cause renal injury. Among phospholipid fatty acids, the ratio of oleic to linoleic acids (18:1/18:2) was strongly linked to both glomerular (r = 0.83, P less than 0.01) and tubulo-interstitial (rr = 0.80, P less than 0.01) injury, suggesting a possible role for a relative essential fatty acid deficiency in renal injury. There were also strong, negative associations between eicosapentaenoic acid levels and glomerular (r = -0.63, P less than 0.01) and tubulointerstitial (r = -0.71, P less than .01) injury. Altogether, these results suggest that specific abnormalities in renal lipid metabolism may be important in the pathogenesis of chronic, progressive renal injury.     

High linoleic acid diets ameliorate diabetic nephropathy in rats

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11% fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gamma linolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (FO; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF1 alpha to thromboxane B2 (TXB2), the stable metabolites of PGI2 and TXA2, respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF1 alpha/TXB2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.     

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).     

Polyunsaturated fatty acids and renal fibrosis: pathophysiologic link and potential clinical implications

The role of polyunsaturated fatty acids in renal fibrosis. Several studies suggest a close relationship between polyunsaturated fatty acids (PUFA) and renal inflammation and fibrosis, which are crucial stages in chronic kidney disease (CKD). Beneficial effects of n-3 PUFA on the course of experimental and human nephropathies have been reported. PUFA can ameliorate chronic, progressive renal injury beyond the simple reduction of serum lipid levels. These pleiotropic effects of PUFA are due to their properties of interfering with the synthesis of a variety of inflammatory factors and events, through effects related both to the modulation of the balance of n-6 and n-3-derived eicosanoids and to direct action on the cellular production of the major cytokine mediators of inflammation and on endothelium function. The mechanisms by which PUFA can favorably interfere with some stages in renal fibrosis processes, such as mesangial cell activation and proliferation and extracellular matrix protein synthesis, include the regulation of some pro-inflammatory cytokine production, renin and nitric oxide (NO) systems and peroxisome proliferator-activated receptor gene expression. An optimal n-6/n-3 PUFA ratio dietary intake could offer new therapeutic strategies aimed at interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury. However, further experimental, epidemiological and clinical investigations are needed to confirm the role of PUFA in the renal fibrosis pathway and the natural history of chronic nephropathies.     

Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation

Diets high in n-3 fatty acids appear to have an anti-inflammatory effect, which is thought to be due to decreased macrophage prostaglandin (PG) and thromboxane (Tx) production after incorporation of these fatty acids into cell membrane phospholipids. The effect of n-3 fatty acids incorporation on macrophage monokine release in response to septic stimuli is not well established. Kupffer cells, the fixed macrophages of the liver, were obtained from rats fed diets with fat sources derived from corn oil (CO, control), fish oil (FO, high in n-3 fatty acids), or safflower oil (SO, high in n-6 fatty acids) for 2 or 6 weeks. After exposure to bacterial lipopolysaccharide, Kupffer cells from rats fed FO for 2 or 6 weeks produced less PG and Tx than Kupffer cells from rats fed CO or SO. After 2 weeks of defined diets, interleukin-1 (IL-1) and tumor necrosis factor release were not affected by dietary fat source. In contrast, after 6 weeks of feeding, Kupffer cells from both the FO and the SO groups released less IL-1 and tumor necrosis factor when triggered by lipopolysaccharide than Kupffer's cells from animals fed the control diet that contained CO. These data suggest that altered monokine release from macrophages may contribute to the anti-inflammatory effect of diets high in n-3 fatty acids. Also shown in our results is that prolonged changes in membrane phospholipid content induced by dietary fat source can influence not only PG and Tx production but monokine release as well.     

Brief periods of hyperphagia cause renal injury in the obese Zucker rat

BACKGROUND: Female obese (fa/fa) Zucker rats are maximally hyperphagic from the beginning of access to solid food until 20 weeks of age and die primarily from renal failure. We documented that urinary albumin excretion (UAE) rises early in obese rats during this time of greatest hyperphagia. This study was conducted to examine if this early surge of hyperphagia is critical to the initiation of glomerular damage. METHODS: Three groups of six-week-old rats were used: (a) obese females fed ad libitum (AL-obese), (b) obese females pair fed to lean controls until 21 weeks and then allowed to eat ad libitum until 57 weeks (PF. AL-obese), (c) lean (Fa/Fa) Zucker rats fed ad libitum (AL-lean). Cohorts of AL-obese and PF.AL-obese rats were allowed to continue to death or 57 weeks of age, and the rest were terminated at 21 weeks for renal histology. RESULTS: At 21 weeks, neither PF.AL-obese nor AL-lean rats had elevated UAE or glomerular histopathology. In contrast, glomerular injury was severe in AL-obese rats. UAE increased by 10 and 29 weeks in AL- and PF.AL-obese rats, respectively. Plasma triglycerides increased prior to UAE in both PF. AL- and AL-obese rats. CONCLUSIONS: In obese rats fed ad libitum, hyperphagia is followed within a few weeks by hypertriglyceridemia and then by glomerular injury regardless of when ad libitum feeding is initiated. These events do not occur in lean rats or in obese rats pair fed to lean rats. Protective effects of pair feeding did not extend into the period of ad libitum feeding for PF.AL-obese rats. Hyperphagia quickly initiates glomerular injury in obese female Zucker rats.     

Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease

BACKGROUND: Conjugated linoleic acid (CLA) describes positional isomers of linoleic acid (LA). Experimental health benefits of CLA include amelioration of malignancy and inflammatory disease and reduction of adiposity. The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable to dietary modification. We studied CLA supplementation in the modification of inflammatory outcomes in the Han:SPRD-cy rat. METHODS: Male offspring of Han:SPRD-cy heterozygotes were fed diets, using corn oil or corn oil with a CLA enriched oil (1% of diet by weight as CLA). After 8 weeks, measurements included renal function and morphometry, ex vivo release of renal prostaglandin E2 (PGE2), and renal and hepatic tissue fatty acid profiles. RESULTS: Urine creatinine was significantly higher in PKD animals fed CLA (P = 0.004), but differences in serum creatinine and creatinine clearance did not quite reach significance in PKD animals. CLA feeding reduced interstitial inflammation (P < 0.001), fibrosis (P = 0.03), and renal PGE2 release (P = 0.02). Cystic change and oxidized low-density lipoprotein (LDL) staining did not change significantly. CLA feeding produced increased renal and hepatic CLA isomers. Hepatic, but not renal, LA proportion was reduced on the CLA diet. The renal proportion of the PGE2 precursor, arachidonic acid (AA), was not changed by diet, but hepatic AA proportion increased significantly with CLA feeding (P= 0.009). CONCLUSION: CLA reduces renal production of PGE2, without reduced availability of the precursor fatty acid, AA. Short-term feeding of CLA to Han:SPRD-cy rats also has significant renal anti-inflammatory and antifibrotic effects. As inflammation and fibrosis are important components of the progression of chronic renal injury, CLA may be a useful agent in dietary amelioration of renal disease.     

Dietary lipids,prostaglandin E2 levels,and tooth movement in alveolar bone of rats

Summary A previous study showed that certain dietary lipids can alter arachidonic acid concentrations in alveolar bone. Because arachidonic acid is a precursor of prostaglandin (PG) E₂, which is known to play an important role in orthodontic tooth movement, the purpose of the present study was to determine the effect of dietary lipids on PGE₂ levels and tooth movement. Two groups of male Sprague-Dawley rats (20/group) were fed nutritionally adequate purified diets containing 10% corn oil (group I, rich in n-6 fatty acids) or 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (group II rich in n-3 fatty acids). After 5 weeks of feeding the diets, orthodontic force of 56 g was applied to the maxillary incisors to tip them distally. Prior to killing the rats at day 4 and 8 of orthodontic force application, tooth movement was measured by computerized image analysis. Premaxillae were dissected out free of soft tissue and incisors. The alveolar bone was frozen in liquid nitrogen, pulverized, and lipids were extracted. The concentrations of arachidonic acid and fatty acid composition of total phospholipids were measured by gas chromatography. PGE₂ levels were measured by enzyme immunoassay. Arachidonic acid and PGE₂ concentration were significantly lower (P < 0.001) in alveolar bone of rats in group II than in group I. The tooth movement was also significantly lower (P < 0.02) in group II than in group I at both 4 and 8 days. The results suggest that PGE₂ levels in alveolar bone and orthodontic tooth movement can be affected by the type of dietary fat.Presented in part for the Hatton Award Competition at the International Association for Dental Research Meeting, Chicago, Illinois, March 10–14, 1993.