Plasma levels of one-carbon metabolism nutrients in women with anorexia nervosa.

OBJECTIVE: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness. METHOD: We compared plasma levels of one-carbon metabolism nutrients across women with active AN (AN-Active: n = 53), in remission from AN (AN-Remitted: n = 40), or who had no eating-disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre- to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating-disorder symptoms were assessed by interview and self-report. RESULTS: Compared to NED individuals, AN-Active individuals exhibited significantly elevated B12 and (less-reliably) betaine. In AN-Active individuals, lower BMI was associated with higher B12. DISCUSSION: The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects.

Parenteral amino acid supplementation with high-dose insulin prevents hypoaminoacidemia during cardiac surgery.

OBJECTIVES: Surgery triggers a stress response that produces insulin resistance and hyperglycemia. During cardiac surgery, the administration of high-dose insulin along with dextrose titration maintains normoglycemia, but dramatically decreases plasma amino acids (AAs) compared with preoperative fasting levels. Hypoaminoacidemia limits protein synthesis and prevents anabolic responses after surgery. We investigated whether parenteral infusion of AAs during and immediately after cardiac surgery would prevent hypoaminoacidemia in patients who receive high-dose insulin therapy. METHODS: Sixteen patients undergoing coronary artery bypass grafting surgery were randomly allocated to receive AAs with % kcal equivalent to either 20% (n = 8) or 35% (n = 8) of their measured resting energy expenditure (REE). Insulin was infused at a constant rate of 5 mU/(kg × min), whereas dextrose was titrated to maintain normoglycemia during and until 5 h after surgery. Plasma AA concentrations were measured at baseline before and after surgery. RESULTS: Compared with the 20% AA group after surgery, AA concentrations were significantly higher in the 35% AA group for 12 of 20 AAs (P < 0.032), including all branched-chain AAs. In the 20% AA group, total essential AAs decreased by 21% and nonessential AAs decreased by 14% after surgery compared with preoperative fasting levels. In contrast, giving 35% AAs prevented this unfavorable decrease in AAs, and in fact allowed for a 23% and 12% increase in essential and nonessential AAs, respectively. CONCLUSIONS: AA supplementation at 35% REE, but not 20% REE, can effectively prevent hypoaminoacidemia caused by high-dose insulin therapy during cardiac surgery.

Association between pre-breeding metabolic profiles and reproductive performance in heifers and lactating dairy cows.

Lactating cows and nulliparous heifers are in distinctive and unique physiological conditions when they are approaching the planned time of breeding, at approximately 60 days in milk and 13-15 months of age, respectively. This study aimed to profile the metabolic milieu in heifers (N = 14) and lactating cows (N = 15) in the weeks leading up to planned time of breeding. All cows were followed for a period of 15 weeks, from 3 weeks pre-calving to 12 weeks post-calving, while heifers were monitored for a period of 4 weeks leading up to the tentative week of breeding (pre-breeding period). For data analysis, we further divided cows into primiparous (N = 8) and multiparous (N = 7) cows owing to the significant difference in their milk yield. Assessment of reproductive performance showed that primiparous and multiparous cows tended to have lower pregnancy rates compared to heifers (P < 0.1). Plasma concentrations of ß-hydroxybutyric acid were about 2-fold higher in multiparous cows than those of heifers in the week leading up to planned time of breeding (P < 0.05). Total bile acid levels during the pre-breeding period were higher in all lactating cows compared to heifers (P < 0.05) and glucose levels were lower in lactating cows (P < 0.05). Triglyceride concentrations were lowest in multiparous cows compared to both primiparous cows and nulliparous heifers (P < 0.05). In addition, lactating cows had higher concentrations of total-cholesterol and the high-density lipoprotein and low-density lipoprotein compared to heifers (P < 0.05). Conversely, concentrations of very low-density lipoprotein were lower in multiparous cows than primiparous cows and nulliparous heifers (P < 0.05). There were no differences in plasma glutathione levels, as measured by liquid chromatography-tandem mass spectrometry, between the groups, but the ferric reducing ability of plasma was higher in lactating cows compared to heifers (P < 0.05). These data establish the differences in the profile of metabolic and oxidative markers during the period approaching planned time of breeding in lactating cows compared to nulliparous heifers. As certain metabolites in the plasma have been shown to be represented in the ovarian follicular microenvironment, the unique profiles may influence reproductive performance in dairy cattle in different physiological stages.

Hyperinsulinemic-normoglycemic clamp administered together with amino acids induces anabolism after cardiac surgery.

Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-2H2]glucose and l-[1-13C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 µmol·kg-1·h-1, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 µmol·kg-1·min-1, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.

Experimental colitis and malnutrition differentially affect the metabolism of glutathione and related sulfhydryl metabolites in different tissues.

PURPOSE: Inflammatory bowel diseases (IBD) are characterized by severe inflammation within the gastrointestinal (GI) tract. This inflammation is known to drive the catabolism of protein in the affected tissue and modulate systemic protein metabolism. Yet despite the established increase in oxidative stress and changes in protein catabolism, little is known as to the effects of IBD on metabolism of glutathione (GSH) and related metabolites. The aim of this study was to conduct a comprehensive analysis of the response of GSH and related sulfhydryl metabolites to malnutrition and GI inflammation. We hypothesized that the inflammatory stress of colitis would decrease the concentration and the synthesis of GSH in various tissues of well-nourished piglets. Additionally, the superimposition of malnutrition on colitis would further decrease glutathione status. METHODS: Healthy, well-nourished piglets were compared to those receiving dextran sulphate sodium-induced, a macronutrient-restricted diet or both. The synthesis of GSH was determined by primed constant infusion of [(15)N,(13)C2]glycine and tandem mass spectrometry analysis. Additionally, the concentrations of GSH and related sulfhydryl metabolites were also determined by UHPLC-tandem mass spectrometry-a novel analytic technique. RESULTS: In healthy piglets, GSH synthesis was highest in the liver, along with the concentrations of both cysteine and γ-glutamylcysteine. Piglets with colitis had decreased synthesis of GSH and decreased concentrations of GSH, cysteine and γ-glutamylcysteine in the distal colon compared to healthy controls. Additionally, there was no change with superimposition of malnutrition on colitis in the distal colon. CONCLUSION: Synthesis and metabolism of GSH are uniquely regulated in each tissue. Colitis, independent of nutrition, compromises GSH status and the concentration of cysteine in the distal colon of piglets with GI inflammation. The techniques developed in this study have translational applications and can be scaled for use in clinical investigation of GI inflammation.

Glucose and insulin administration while maintaining normoglycemia inhibits whole body protein breakdown and synthesis after cardiac surgery.

We investigated the effect of insulin administered as part of a hyperinsulinemic-normoglycemic clamp on protein metabolism after coronary artery bypass grafting (CABG) surgery. Eighteen patients were studied, with nine patients in the control group receiving standard metabolic care and nine patients receiving insulin (5 mU·kg(-1)·min(-1)). Whole body glucose production, protein breakdown, synthesis, and oxidation were determined using stable isotope tracer kinetics (l-[1-(13)C]leucine, [6,6-(2)H2]glucose) before and 6 h after the procedure. Plasma amino acids, cortisol, and lactate were also measured. Endogenous glucose production (preoperatively 10.0 ± 1.6, postoperatively 3.7 ± 2.5 µmol·kg(-1)·min(-1); P = 0.0001), protein breakdown (preoperatively 105.3 ± 9.8, postoperatively 85.2 ± 9.2 mmol·kg(-1)·h(-1); P = 0.0005) and synthesis (preoperatively 88.7 ± 8.7, postoperatively 72.4 ± 8.4 mmol·kg(-1)·h(-1); P = 0.0005) decreased in the presence of hyperinsulinemia, whereas both parameters remained unchanged in the control group. A positive correlation between endogenous glucose production and protein breakdown was observed in the insulin group (r(2) = 0.385). Whole body protein oxidation and balance decreased after surgery in patients receiving insulin without reaching statistical significance. In the insulin group the plasma concentrations of 13 of 20 essential and nonessential amino acids decreased to a significantly greater extent than in the control group. In summary, supraphysiological hyperinsulinemia, while maintaining normoglycemia, decreased whole body protein breakdown and synthesis in patients undergoing CABG surgery. However, net protein balance remained negative.

The anabolic effect of perioperative nutrition depends on the patient's catabolic state before surgery.

OBJECTIVE: We tested the hypothesis that the anabolic effect of hypocaloric, isonitrogenous nutrition in patients undergoing colorectal surgery depends on the patient's preoperative catabolic state. BACKGROUND: Although there is evidence to suggest that total parenteral nutrition more effectively spares protein in depleted than in nondepleted cancer patients, the influence of preoperative catabolism on the anabolic effects of hypocaloric nutrition in patients undergoing elective surgery is unknown. METHODS: Seventeen patients undergoing colorectal surgery received intravenous infusion of glucose with amino acids. Feeding was administered over 72 hours, from 24 hours before until 48 hours after surgery. Glucose provided 50% of the patient's measured resting energy expenditure. Amino acids provided 20% of the resting energy expenditure. Whole-body leucine balance (difference between the incorporation of leucine into protein = protein synthesis and endogenous leucine release = proteolysis) was determined using L-[1-(13)C]leucine kinetics before and 2 days after surgery. We analyzed the association between the postoperative increase in leucine balance and the following factors: preoperative leucine balance, protein breakdown, weight loss, oxygen consumption, circulating concentrations of glucose, free fatty acids, insulin, glucagon, cortisol, albumin, age, duration of surgery, and blood loss. RESULTS: Of 6 potentially relevant variables, 4 (weight loss, protein breakdown, albumin, and cortisol) were removed because they were not significant during the stepwise linear regression procedure. Leucine balance and age were the remaining 2 factors that remained with the final regression model: Δleucine balance = 19.1 - (0.20 × age [years]) - (0.58) × leucine balance(preOP)). CONCLUSIONS: We demonstrate a significant association between the degree of preoperative catabolism, the patient's age, and the anabolic effect of hypocaloric nutrition (ClinicalTrials.gov registration ID: NCT01414946).

High-dose insulin therapy reduces postoperative liver dysfunction and complications in liver resection patients through reduced apoptosis and altered inflammation.

CONTEXT: An exaggerated inflammatory response in patients undergoing major liver resection coupled with poor nutrition diminishes liver regenerative capacity and increases the risk of postoperative complications. OBJECTIVES: Our objective was to evaluate the biological context leading to better clinical outcomes in patients undergoing liver resection coupled with hyperinsulinemic-normoglycemic clamp vs. standard care (insulin sliding care). DESIGN AND SETTING: This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center. PATIENTS AND INTERVENTION: Thirty consenting patients participating in a randomized clinical trial for liver resection received either hyperinsulinemic-normoglycemic clamp technique with 24-h preoperative carbohydrate load (intervention) or standard glucose control through insulin sliding scale treatment (control). MAIN OUTCOME MEASURES: Liver biopsies and plasma samples were taken at various time points before and after surgery. Primary measures included mRNA quantitation for genes related to insulin signaling, inflammation, and proliferation; proinflammatory cytokines at various time points; and liver function markers. These measurements were associated with clinical outcomes. RESULTS: The hyperinsulinemic-normoglycemic clamp technique reduced postoperative liver dysfunction, infections, and complications. Markers of energy stores indicated higher substrate availability. Cytokine expression pattern was altered (TNF-α, IL-8, monocyte chemoattractant protein-1, IL-6, IL-10, and C-reactive protein). Apoptosis was markedly reduced, whereas the complement system was unaltered. CONCLUSION: The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears to be linked with higher substrate availability and altered cytokine secretion profile and may provide a long-term benefit of this therapy on liver resection patients.

Dietary soy protein benefit in experimental kidney disease is preserved after isoflavone depletion of diet.

Soy diet ameliorates renal injury in the Han:SPRD-cy rat. The relative roles of protein, isoflavones and changes in polyunsaturated fatty acid (PUFA) status are not determined. We fed male Han:SPRD-cy heterozygotes casein (C), high isoflavone soy protein (HIS), alcohol-extracted low isoflavone soy protein (LIS) or mixed soy protein diet (MIS). LIS and MIS were associated with a small decrease in animal weight compared with HIS or C. Soy diets preserved normal renal function and reduced relative renal weight (10.9-14.6 g/kg, cf. 23.6, P < 0.001), scores for cystic change (0.168-0.239, cf. 0.386, P < 0.05), fibrosis (0.013-0.015, cf. 0.032, P < 0.05), tissue oxidized LDL content (0.012-0.021, cf. 0.048, P < 0.05), inflammation (8.5-12.9, cf. 31.2, P < 0.05) and epithelial cell proliferation (6.5-13.8, cf. 26.3, P < 0.05). In post hoc testing, LIS produced a greater reduction in relative renal weight, cystic change and epithelial proliferation, whereas HIS produced a significantly greater reduction in oxidized-LDL. Soy diets were associated with increased hepatic content of 18C PUFA (P < 0.001). LIS and HIS diets were associated with a small increase in body fat content (P < 0.001). Alcohol-extracted soy protein retains its major protective effects in this model with subtle differences attributable to isoflavones.

Dietary conjugated linoleic acid renal benefits and possible toxicity vary with isomer, dose and gender in rat polycystic kidney disease.

Conjugated linoleic acid (CLA) is anti-proliferative and anti-inflammatory in the Han:SPRD-cy rat model of kidney disease. We used different doses of CLA and examined effects on renal histological benefit, the renal PPARgamma system and hepatic and renal levels of CLA isomers. Male and female offspring of Han:SPRD-cy heterozygotes were fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks before dual-energy X-ray absorptiometry, harvest of renal and hepatic tissue for histologic and lipid analysis. Both CLA diets reduced body fat content in both genders but did not change lean body mass. CLA produced a dose dependent reduction in female renal cystic change. CLA reduced fibrosis, but this reduction was significantly less with higher dose in males. CLA reduced macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. Serum creatinine rose significantly in female animals fed CLA diets. CLA treatment did not change PPARgamma activation. A significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects was identified. CLA reduces histologic renal injury in the Han:SPRD-cy rat model probably inversely proportionate to c9,t11 renal content. Possible functional CLA toxicity at high dose in female animals warrants further exploration.

Dietary conjugated linoleic acid decreases adipocyte size and favorably modifies adipokine status and insulin sensitivity in obese, insulin-resistant rats.

Conjugated linoleic acids (CLA) have been shown to alter adiposity in some species with varying effects on insulin resistance. The objective of this 8-week study was to investigate the effects of feeding a CLA mixture (1.5%, wt/wt) on adipocyte size, insulin sensitivity, adipokine status, and adipose lipid composition in fa/fa vs lean Zucker rats. The fa/fa CLA-fed rats had smaller adipocytes and improved insulin sensitivity compared with fa/fa rats fed the control diet. Conjugated linoleic acids did not affect select markers of adipose differentiation, lipid filling, lipid uptake, or oxidation. Dietary CLA, compared with the control diet, reduced circulating leptin and elevated fasting serum adiponectin concentrations in fa/fa rats. Adipose resistin messenger RNA levels were greater in fa/fa CLA-fed rats compared with fa/fa control rats. CLA did not markedly alter adipose phospholipid fatty acid composition, and the changes in the triacylglycerol fatty acid composition reflected a lower delta-9 desaturase index of CLA-fed vs control-fed rats. In conclusion, CLA reduced adipocyte size and favorably modified adipokine status and insulin sensitivity in fa/fa Zucker rats.

Conjugated linoleic acid reduces hepatic steatosis, improves liver function, and favorably modifies lipid metabolism in obese insulin-resistant rats.

CLA has been shown to induce or suppress excess liver lipid accumulation in various animal models. Interestingly, the state of insulin resistance may be an important modulator of this effect. The objective of the current study was to determine how feeding a dietary CLA mixture would affect liver lipid accumulation in insulin-resistant/obese and lean rats in relation to liver function, lipidemia, liver TAG and phospholipid FA composition, and expression of hepatic markers of FA transport, oxidation, and synthesis. Six-week-old fa/fa and lean Zucker rats (n = 20/genotype) were fed either a 1.5% CLA mixture or a control diet for 8 wk. CLA supplementation reduced liver lipid concentration of fa/fa rats by 62% in concurrence with improved liver function (lower serum alanine aminotransferase and alkaline phosphatase) and favorable modification of the serum lipoprotein profile (reduced VLDL and LDL and elevated HDL) compared with controlfed fa/fa rats. The fa/fa genotype had two-thirds the amount of CLA (as % total FA) incorporated into liver TAG and phospholipids compared with the lean genotype. In both genotypes, CLA altered the hepatic FA profile (TAG greater than phospholipids) and these changes were explained by a desaturase enzyme index. Liver-FA-binding protein and acyl CoA oxidase, markers of FA transport and oxidation, respectively, were expressed at higher levels in CLA-fed fa/fa rats. In summary, these results illustrate a strong relationship between the state of insulin resistance and liver lipid metabolism and suggest that CLA acts to favorably modify lipid metabolism in fa/fa Zucker rats.

Effects of flaxseed derivatives in experimental polycystic kidney disease vary with animal gender.

Flaxseed derivatives, including both oil and flax lignan, modify progression of renal injury in animal models, including Han:SPRD-cy polycystic kidney disease (PKD). Gender is a significant factor in the rates of progression of many forms of human renal disease, but the role of gender in the response to nutrition intervention in renal disease is unexplored. In this study, male and female Han:SPRD-cy rats or normal littermates were fed either corn oil (CO) or flax oil (FO) diets, with or without 20 mg/kg of the diet flax lignan secoisolaricinoresinol dyglycoside (SDG). Renal injury was assessed morphometrically and biochemically. Renal and hepatic PUFA composition was assessed by GC and renal PGE2 release by ELISA. FO preserved body weight in PKD males, with no effect in females. SDG reduced weight in both normal and PKD females. FO reduced proteinuria in both male and female PKD. FO reduced cystic change and renal inflammation in PKD males but reduced cystic change, fibrosis, renal inflammation, tissue lipid peroxides, and epithelial proliferation in PKD females. SDG reduced renal inflammation in all animals and lipid peroxides in PKD females. A strong interaction between SDG and FO was observed in renal FA composition of female kidneys only, suggesting increased conversion of C18 PUFA to C20 PUFA. FO reduced renal release of PGE2 in both genders. Gender influences the effects of flaxseed derivatives in Han:SPRD-cy rats. Gender-based responses to environmental factors, such as dietary lipid sources and micronutrients, may contribute to gender-based differences in disease progression rates.

Dietary soy protein attenuates renal disease progression after 1 and 3 weeks in Han:SPRD-cy weanling rats.

Compared with casein, dietary soy protein slows disease progression in animal models of chronic renal injury. To determine whether dietary soy protein feeding can alter early disease progression, male Han:SPRD-cy rats (n = 87) in a very early stage of chronic kidney disease were fed soy protein compared with casein-based diets for 1 or 3 wk. Kidneys were assessed for fibrosis, cyst growth, fatty acid composition and prostaglandin E(2) (PGE(2)) production. Soy protein feeding significantly reduced renal fibrosis by 22% (P = 0.0347) and 38% (P = 0.0102) after 1 and 3 wk of diet, and cyst growth was 34% lower after 3 wk (P < 0.0001). Kidney 18:2(n-6) levels were reduced in normal and diseased rats after as little as 1 wk of consuming the soy protein diet. Dietary soy protein also partially ameliorated the suppression of PGE(2) production observed in diseased kidneys. Compared with diseased kidneys from casein-fed rats, ex vivo PGE(2) release was 31-32% higher after 1 (P = 0.0281) and 3 (P = 0.0189) wk of dietary soy protein consumption. Hence, the first signs of a beneficial soy protein effect were observed after 1 wk of feeding, with further improvements evident after 3 wk. These data demonstrate that dietary soy protein compared with casein delays disease progression in an early stage of chronic kidney disease.

Conjugated linoleic acid reduces parathyroid hormone in health and in polycystic kidney disease in rats.

BACKGROUND: Feeding conjugated linoleic acid (CLA) is reported to reduce prostaglandin E(2) synthesis, which is required for parathyroid hormone (PTH) release. OBJECTIVE: This study was undertaken to determine whether CLA would suppress hyperparathyroidism and the resulting high-turnover bone disease in a rat model of polycystic kidney disease (PKD). DESIGN: Outcome measurements were conducted after 8 wk of feeding diets supplemented with and without CLA (1% of dietary fat) to Han:SPRD-cy male rats (n = 52). PTH, bone formation, and resorption were assessed in addition to femur bone mass with use of dual-energy X-ray absorptiometry. RESULTS: CLA feeding resulted in attenuation of PTH concentrations in both PKD-affected and nonaffected rats (by 60%) but did not significantly alter bone formation and resorption. CONCLUSION: Reduction in PTH may open possibilities for CLA as an adjunctive therapy in secondary hyperparathyroidism.

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.

Elevated bone turnover in rat polycystic kidney disease is not due to prostaglandin E2.

Hyperparathyroidism, secondary to renal disease, is thought to cause high bone turnover via prostaglandin E2 (PGE2). Diets high in n-3 fatty acids reduced PGE2. Thus the objective was to compare the effect of diets high in n-6 and n-3 fatty acids on hyperparathyroidism, bone turnover, and PGE2 in Han:SPRD- cy rats that develop polycystic kidney disease (PKD). Weanling male rats ( n=58) were randomized to diets made with either corn or flaxseed oil (5%) for 8 weeks, followed by measurement of plasma parathyroid hormone (PTH), osteocalcin, urinary N-telopeptide (NTX), and ex vivo release of PGE2from femur. Plasma PTH was elevated ( P<0.01) as a result of PKD. Mean values for plasma osteocalcin and urinary NTX were elevated ( P<0.01) by PKD but not altered by diet. In contrast, values for PGE2 were lowest in the PKD rats fed flaxseed oil compared with PKD rats fed corn oil and compared with non-affected rats fed either oil. Rats with PKD have high-turnover bone disease, likely due to hyperparathyroidism, that is unaffected by feeding corn or flaxseed oils. Since PGE2 release is lower in the presence of high bone turnover, the high bone turnover in evolving rat uremia is not likely to be mediated by PGE2.

Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n-6/n-3 FA ratio in experimental polycystic kidney disease.

As whole flaxseed is beneficial in the treatment of experimental renal disease, we undertook a study to determine whether previously documented benefits of whole flaxseed could be reproduced with dietary low-lignan flax oil (FO), a rich source of alpha-linolenic acid, in experimental polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygous rats were fed a synthetic diet containing FO or corn oil (CO) for 8 wk from the time of weaning. Renal inflammation, fibrosis, proliferation, cystic change, and oxidized-LDL were assessed morphometrically. Hepatic and renal lipid composition was assessed using GC. FO feeding produced hepatic and renal enrichment of n-3 PUFA and an increase in C18:>C18 PUFA ratios (18-carbon PUFA compared to longer-chain PUFA), with a reduction in proportion of hepatic long-chain PUFA. The FO-based diet was associated with lower mean cystic change by 29.7% (P = 0.018), fibrosis by 21.7% (P = 0.017), macrophage infiltration by 31.5% (P < 0.0001), epithelial proliferation by 18.7% (P = 0.0035), and ox-LDL detection by 31.4% (P < 0.0001) in Han:SPRD-cy heterozygotes. Serum creatinine was significantly lower in FO-fed diseased animals. A small hypocholesterolemic effect was noted in all animals fed FO. FO feeding moderates renal injury, modifies the profile of substrates available for elongation to eicosanoid precursors, and inhibits the elongation of C18 PUFA in this model. The consumption of FO-based products may prove a more practical way of obtaining health benefit than attempts to increase dietary content of unrefined seed.