Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel.

Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5:1 (Standard Rodent Chow), and measured the influence of diet on core body temperature (Tb), brown adipose tissue (BAT) mass, fatty acid profiles of BAT, white adipose tissue (WAT) and plasma as well as hypothalamic endocannabinoid and endocannabinoid-like bioactive fatty acid amides during hibernation. Results show feeding a diet high in omega 3 PUFAs, with a more balanced omega 6:3 ratio, increases AGS Tb in torpor. We found the diet-induced increase in Tb during torpor is most easily explained by an increase in the mass of BAT deposits of Balanced Diet AGS. The increase in BAT mass is associated with elevated levels of metabolites DHA and EPA in tissue and plasma suggesting that these omega 3 PUFAs may play a role in thermogenesis during torpor. While we did not observe diet-induced change in endocannabinoids, we do report altered hypothalamic levels of some endocannabinoids, and endocannabinoid-like compounds, during hibernation.

Dynamic interactions of n-3 and n-6 fatty acid nutrients.

Careful handling of data on fatty acid composition is needed when interpreting evidence for the influence of dietary n-3 and n-6 essential fatty acids on brain function and health conditions. The relative dietary supplies of competing n-3 and n-6 nutrients determine the balance of 20- and 22-carbon n-3 and n-6 highly unsaturated fatty acids (HUFA) which accumulate competitively at the 2-position of tissue phospholipids. In turn, the HUFA balance expressed as the %n-6 in HUFA affects the likely intensity of n-6 eicosanoid actions in diverse health conditions. As a result, measures of HUFA balance are important, valid biomarkers for designing and monitoring successful preventive nutrition interventions. Successful interventions must also consider the ability of fatty acid ligands to saturate binding sites of enzymes and receptors and give paradoxical dose-response results.

The influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction.

Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95 % (control) or 60 % (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H(2)O(2) production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CR-induced decreases in ROS production.

The effects of feeding diets containing corn distillers dried grains with solubles, and withdrawal period of distillers dried grains with solubles, on growth performance and pork quality in grower-finisher pigs.

A study was conducted to determine the quantitative effects of feeding amount and withdrawal period of corn distillers dried grains with solubles (DDGS) from the diet on growth performance, carcass quality, and pork fat fatty acid profile. A total of 432 pigs (29.8 +/- 0.2 kg of BW) were randomly allotted to 1 of 9 dietary treatments in a completely randomized arrangement. The 9 treatments were the control (D0), D15-0 wk, D15-3 wk, D15-6 wk, D15-9 wk, D30-0 wk, D30-3 wk, D30-6 wk, and D30-9 wk, where D0, D15, and D30 indicate the dietary content of DDGS (0, 15, and 30%, respectively) and 0 wk, 3 wk, 6 wk, and 9 wk indicate the withdrawal period of DDGS from the diets before slaughter (0, 3, 6, and 9 wk, respectively). A dietary DDGS inclusion rate of 15 or 30%, without or with a withdrawal period, had no effect (P = 0.76) on ADG, ADFI, and G:F, except for a slight reduction (0.87 vs. 0.92 kg/d; P < 0.05) in ADG when pigs received the D30-0 wk treatment compared with the D0 treatment. Carcass quality, LM quality, and Japanese fat color scores for backfat and belly fat were not affected by dietary DDGS content (backfat, P = 0.47; belly fat, P = 0.17) or withdrawal period (backfat, P = 0.33; belly fat, P = 0.95). Compared with pigs fed the D0 diet, a smaller belly firmness score was observed (P = 0.04) in pigs that received the D30-0 wk treatment, but belly firmness in pigs fed the other treatments was not different (P = 0.26) from that of pigs fed the D0 diet. Linoleic acid content (C18:2; P < 0.001) and iodine value (IV; P < 0.001) of belly fat increased with increasing dietary DDGS content. Withdrawal of DDGS from the diet for 0 to 9 wk before slaughter resulted in a linear reduction in C18:2 content and the IV of belly fat in pigs fed the D15 diets (C18:2 content: 14.6, 13.3, 12.6, and 10.9%; P = 0.001; IV: 67.3, 64.4, 64.1, and 62.7; P = 0.02; for 0-, 3-, 6-, and 9-wk withdrawal, respectively) and the D30 diets (C18:2 content: 17.3, 16.1, 14.2, and 12.4%; P < 0.001; IV: 71.2, 68.2, 64.5, and 62.7; P < 0.001; for 0-, 3-, 6-, and 9-wk withdrawal, respectively). These results indicate that an inclusion rate of DDGS up to 30% in grower-finisher diets has minor effects on growth performance and that the desired effect of reducing the C18:2 content and IV of pork fat could be elicited in as little as 3 wk after withdrawing DDGS from the diet before slaughter.

Effects of feeding diets containing increasing content of corn distillers dried grains with solubles to grower-finisher pigs on growth performance, carcass composition, and pork fat quality.

Crossbred pigs (n = 512) with an average initial BW of 22.1 +/- 0.54 kg were used to evaluate growth performance, carcass characteristics, and pork fat quality of grower-finisher pigs fed corn-soybean meal diets containing increasing content of distillers dried grains with solubles (DDGS). One of 4 dietary treatments was randomly assigned to each pen within sex. Dietary treatment and sex were the main factors in a 3-phase feeding program (BW = 22 to 53 kg, 53 to 85 kg, and 85 to 115 kg). Dietary treatments consisted of a corn-soybean meal control, or a corn-soybean meal diet containing 10, 20, or 30% DDGS. Overall, increasing the dietary DDGS content had no effect on ADG (P = 0.74), but ADFI was linearly reduced and G:F was linearly increased (P < 0.01). Dressing percentage, LM marbling and firmness, and belly firmness were linearly reduced (P < 0.01), but percentage of fat-free lean was linearly increased (P < 0.05) with increasing dietary DDGS. Subjective LM color score (P = 0.65), drip loss (P = 0.37), and ultimate pH of LM (P = 0.21) were not influenced by dietary DDGS. Japanese color scores for backfat (P = 0.41) and belly fat (P = 0.85) were similar among dietary treatments (P = 0.41). Feeding an increasing content of DDGS linearly increased (P < 0.05) PUFA concentration, particularly linoleic acid (C18:2), in belly fat, backfat, and LM intramuscular fat, but the increase in LM intramuscular fat was smaller in magnitude (P < 0.05) than in backfat and belly fat. Pigs fed an increasing content of DDGS had a linear increase (P < 0.05) in the iodine value of backfat, belly fat, and LM intramuscular fat of 58.4 to 72.4, 61.5 to 72.3, and 54.8 to 57.7, respectively. Oxidation of LM intramuscular fat measured on d 0, 14, 21, and 28 of storage was not affected by dietary treatment. Taste tests for LM showed no effects of diet on flavor, off-flavor (P = 0.36), tenderness (P = 0.66), juiciness (P = 0.58), and overall acceptability (P = 0.52) scores. Similarly, bacon flavor (P = 0.88), off-flavor, crispiness, and overall liking scores were not affected by increasing dietary DDGS, but bacon fattiness (P < 0.01) and tenderness (P < 0.05) scores were linearly reduced. These results showed no negative effects on growth performance or dressing percentage when growing-finishing pigs were fed diets containing up to 30% DDGS, but fat quality may not meet the standards of all pork processors when feeding diets containing more than 20% DDGS.

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells.

Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (omega3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (omega6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the omega3 fatty acids EPA and DHA and of the omega6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of omega3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of omega6 to omega3 fatty acids may be a significant factor in mediating tumor development.

Total fat intake modifies plasma fatty acid composition in humans.

Plasma fatty acid composition reflects dietary fatty acids. Whether the total fat content of the diet alters the fatty acid composition of plasma phospholipid, cholesteryl ester, triacylglycerol and free fatty acids is unknown. To evaluate the effects of low versus high fat diets on plasma fatty acids, a 12-wk, randomized, crossover, controlled feeding trial was conducted in healthy men and women with isoenergic low fat (20% energy) and high fat (45% energy) diets containing constant proportions of fatty acids. Ten subjects consumed one experimental diet for 28 d, their usual diet for 4 wk and the alternate experimental diet for 28 d. Endpoint measures of plasma fatty acids were determined at the end of each experimental period. The effects of the two diets were compared within subjects by analysis of variance. Plasma fatty acids (%) varied in response to total dietary fat with significantly greater total polyunsaturated fat, (n-6) and 18:2(n-6) levels in phospholipids and cholesteryl esters after high fat dietary consumption. The low fat diet was associated with significantly greater total (n-3) fatty acids, 20:5(n-3) and 22:6(n-3) levels in plasma phospholipid fatty acids and cholesteryl esters. Consumption of a low fat diet alters fatty acid patterns in a manner similar to that observed with feeding of (n-3) long-chain fatty acids. This change is likely related to decreased competition for the enzymes of elongation and desaturation, with reduced total intake of 18:2(n-6) favoring elongation and desaturation of available (n-3) fatty acids.

Providers' perceptions of an immunization registry.

OBJECTIVE: To determine providers' perceptions of a statewide immunization registry. DESIGN: Mail survey. SETTING: King County, Washington. METHODS: A random sample of 700 pediatricians, family physicians, and RN/NPs were surveyed. In addition to their perceptions of registries, respondents reported their immunization procedures in the absence of immunization histories. RESULTS: Of 544 eligible participants, 344 returned surveys (63% response rate). Seventy-seven percent of RN/NPs, 60% of pediatricians and 47% of family physicians (p < 0.001) responded that they thought that electronic immunization registries represented the "best chance to solve the lack of documentation problem." Fifty-seven percent of RN/NPs, 61% of pediatricians, and 43% of family physicians reported that the incompleteness of registry data presented a barrier to their using one (p < 0.01). Fewer than 14% of all specialties had concerns about potential compromises of patient confidentiality as a result of registries, although RN/NPs were more concerned about this possibility than both pediatricians and family physicians (p = 0.02). In a multivariate analysis, pediatricians were 43% less likely (p = 0.15) and family physicians were 73% less likely (p < 0.01) than RN/NPs to think registries are the solution to the lack of documentation problem. Familiarity with the existing registry was associated with a significant decrease in the likelihood of thinking that registries are the solution (OR .49 [.26-.90]) and an increase in the likelihood of thinking that registries will take a long time to become of practical value (OR 2.21 [1.09-4.29]). CONCLUSIONS: Specialties differ with respect to their opinions regarding the promise immunization registries hold. Immunization registries appear to be well regarded in theory but may disappoint in practice. Incompleteness of immunization data may be the largest obstacle for registries to overcome.

Essential fatty acid deficiency and predisposition to lung disease in cystic fibrosis.

UNLABELLED: Essential fatty acid (EFA) deficiency is a predisposing factor for pulmonary infection with Staphylococcus aureus and Pseudomonas aeruginosa, the two major pathogenic microorganisms in cystic fibrosis (CF). OBJECTIVE: The goal of this study was to investigate the essential fatty acid status of CF patients from infancy to 20 years old. MATERIALS AND METHODS: Plasma fatty acid profiles for phospholipid (PL) were determined for cord (n = 6), 4 months (n = 40), 16 months (n = 25), 3 y (n = 8), 5-10 y (n = 10), and 10-20 y (n = 10) aged CF patients and compared to their respective control; cord (n = 22), 1-36 months (n = 38) and adult (n = 100). Significance was established by Student's t-test (p < 0.05). RESULTS: The plasma PL fatty acid profile for all CF patients, except cord, revealed consistent deficiency in omega 3 and omega 6 EFAs. These deficiencies were most marked at infancy and more pronounced for patients with meconium ileus. CONCLUSIONS AND RELEVANCE: EFA deficiency may contribute to the predisposition of CF infants to develop respiratory disease and to the excess cytotoxic activity found in bronchoalveolar lavage fluid at 2 months of age in the majority of screened infants.

Liposomes modulate Kupffer cell endotoxin response.

OBJECTIVES: To test the hypothesis that pretreatment with liposomes enriched with the omega 3 fatty acid docosahexaenoic acid (22:6 omega 3) will alter the Kupffer's cell and systemic cytokine (tumor necrosis factor and interleukin-6) response to endotoxin challenge, and to demonstrate alterations in Kupffer's cell phospholipid fatty acid composition after in vivo liposome treatment. DESIGN: Nonrandomized controlled laboratory investigation in Wistar rats. INTERVENTIONS: Animals were assigned to three pretreatment groups: no liposomes; liposomes, 100 mg/kg; or liposomes, 400 mg/kg given by bolus intravenous injection with the animals under inhalation anesthesia. Eighteen hours after liposome treatment, each group was challenged with Escherichia coli lipopolysaccharide (3 mg/kg intraperitoneally in 10 mL of lactated Ringer's solution) or lactated Ringer's solution only. In a separate set of experiments, Kupffer's cells were obtained from animals pretreated with liposome, 400 mg/kg, or controls and challenged with lipopolysaccharide (1, 100, or 10(4) ng/mL) in vitro. OUTCOME MEASURES: Serum and Kupffer's cell supernatant tumor necrosis factor and interleukin-6 bioactivity, Kupffer's cell phospholipid fatty acid composition, survival, and liver histologic findings. RESULTS: In vivo liposome pretreatment (400 mg/kg) resulted in significant increases in serum tumor necrosis factor and interleukin-6 levels 90 minutes after intraperitoneal lipopolysaccharide challenge (P < .05 vs no liposomes). Kupffer's cells isolated from liposome-treated animals (400 mg/kg) compared with untreated controls release significantly more tumor necrosis factor and interleukin-6 after lipopolysaccharide stimulation in vitro in a dose-dependent response (P < .05). Liposome treatment increased total polyunsaturated fatty acid, total omega 3, and docosahexaenoic acid 22:6 omega 3 content in Kupffer's cell phospholipids compared with untreated controls. Survival 24 hours after lipopolysaccharide challenge was reduced by liposome (400 mg/kg) pretreatment (P < .05 by chi 2 test). Livers from each treatment group demonstrated focal areas of hepatocyte necrosis and inflammatory cells. CONCLUSION: Liposome pretreatment increases the circulating and Kupffer's cell cytokine response to endotoxemia, increases Kupffer's cell polyunsaturated fatty acid content, and is associated with reduced survival.

Essential fatty acid deficiency profiles in idiopathic immunoglobulin A nephropathy.

The profiles of fatty acids (FAs) of plasma phospholipids (the compartment reflecting the essential FA status of tissue lipids), nonesterified FAs (the precursor pool for autacoid synthesis), urine protein excretion, and glomerular filtration rate were measured before and after supplementation with fish oil in 15 patients with immunoglobulin A nephropathy. In the FA profiles, there was deficient 18:3 omega 3 (alpha-linolenic acid), the parent compound of omega 3 polyunsaturated FA, and deficient chain elongation products of both omega 3 and omega 6 polyunsaturated FAs with replacement by saturated and monounsaturated short-chain, odd-chain, and branched-chain FAs, producing significant loss of omega 3 FA. These alterations indicate nutritional or functional (omega 3) and metabolic (omega 6) deficiencies. Additionally, the mean melting point of the FAs was significantly increased, implying an inherent decrease in cell membrane fluidity. Enhancement of 20: 5 omega 3 (eicosapentaenoic acid) and 22:6 omega 3 (docosahexaenoic acid) and suppression of 20:4 omega 6 (arachidonate) after supplementation with fish oil were accompanied by important decreases in proteinuria and improved glomerular filtration rate. Omega-3 polyunsaturated FAs may favorably influence immunoglobulin A nephropathy through a modulation of the pathologic actions of the omega 6 eicosanoids and other diverse actions on various mediators produced by an initial immune injury.

Abnormal plasma lipids of patients with Retinitis pigmentosa.

Retinitis pigmentosa (RP) is a hereditary retinal degeneration of unknown etiology, resulting in progressive night blindness, loss of peripheral vision, abnormal retinal pigmentation and reduced electroretinographic response. Docosahexaenoic acid (22:6 omega 3) is found in high concentration in the rod outer segment membranes of the retina. Previous reports of low 22:6 omega 3 in blood lipids or phospholipids in RP patients prompted us to evaluate the complete fatty acid (FA) profiles of plasma phospholipids (PL), cholesteryl esters, triglycerides (TG) and nonesterified fatty acids (NEFA) in ten patients with RP. In the PL fraction, we found significantly depressed levels of 22:6 omega 3, 22:5 omega 3, total omega 3, 22:5 omega 6, 22:4 omega 6 and total omega 6 polyunsaturated FA (PUFA), and elevated total saturated acids. Plasma TG showed normal levels of PUFA, normal total saturated FA and total monounsaturated FA. The NEFA fraction showed significant elevation in total saturated FA with depressed total omega 6 PUFA. Evidence is accumulating mulating that RP is associated with abnormal PUFA and lipid metabolism.