We hypothesized that chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, to young adult male rats would prevent/ameliorate fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Eighty 12–14-week-old young adult male Fischer 344 rats received either: (1) sham irradiation, (2) 40 Gy of fractionated whole-brain irradiation delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation plus continuous administration of 15 mg/L of ramipril in the drinking water starting 3 days before irradiation, or (4) fractionated whole-brain irradiation plus ramipril. Cognitive function was assessed using a perirhinal cortex-dependent version of the novel object recognition task 26 weeks after irradiation. Microglial activation was determined in the perirhinal cortex and the dentate gyrus of the hippocampus 28 weeks after irradiation using the ED1 antibody. Neurogenesis was assessed in the granular cell layer and subgranular zones of the dentate gyrus using a doublecortin antibody. Fractionated whole-brain irradiation led to: (1) a significant impairment in perirhinal cortex-dependent cognitive function, (2) a significant increase in activated microglia in the dentate gyrus but not in the perirhinal cortex, and (3) a significant decrease in neurogenesis. Continuous administration of ramipril before, during, and after irradiation prevented the fractionated whole-brain irradiation-induced changes in perirhinal cortex-dependent cognitive function, as well as in microglial activation in the dentate gyrus. Thus, as hypothesized, continuous administration of the angiotensin-converting enzyme inhibitor, ramipril, can prevent the fractionated whole-brain irradiation-induced impairment in perirhinal cortex-dependent cognitive function.

Background: Genetic variants in the FADS cluster are determinants of arachidonate synthesis, but their role in eicosanoid generation remains unclear. Results: FADS SNP, rs174537 is associated with leukotriene B 4 and 5-HETE production from stimulated human blood. Conclusion: A FADS SNP affects the synthesis of 5-lipoxygenase products. Significance: FADS variation may influence inflammation via eicosanoid biosynthesis.

Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

BackgroundIngestion of polyunsaturated fatty acids (PUFAs) has been proposed to influence several chronic diseases including coronary heart disease (CHD) and type-2 diabetes (T2D).There is strong evidence that omega-3 (n-3) PUFAs provide protection against CHD and biomarkers of atherosclerosis. In contrast, there is more limited and inconsistent data for T2D. Few studies have examined the impact of n-3 PUFA-containing botanical oils on T2D.MethodsFifty-nine subjects with early-stageT2D or metabolic syndrome participated in an 8-week, randomized, single-blind, parallel intervention study and were provided PUFA-containing oils. Individuals received either corn oil (CO), a botanical oil (BO) combination (borage [Borago officinalis L.]/echium oil [Echium plantagineum L.]) or fish oil (FO). The BO combination was enriched in alpha-linolenic, gamma-linolenic, and stearidonic acids and the FO in eicosapentaenoic and docosahexaenoic acids. Serum fatty acids and other serum lipids(triglycerides and total, HDL and LDL cholesterol), as well as markers of inflammation (leptin, and C-reactive protein) and glucose regulation (glucose and hemoglobin A1c) were assessed from fasting participants at baseline and after the intervention.ResultsCompliance was verified by expected increases in specific PUFAs in each of the three oil arms. Participants in the CO group showed no differences in serum lipids, markers of inflammation or glucose regulation between pre- and post-treatment measures. Supplementation with BO significantly lowered total and LDL cholesterol levels and FO reduced serum triglycerides, hemoglobin A1c and increased HDL-cholesterol.ConclusionShort-term dietary supplementation with BO and FO improved biomarkers associated with T2D/metabolic syndrome.Trial registrationClinicaltrial.gov NCT01145066

Depression and altered serum lipids in cynomolgus monkeys on a Western diet. Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a ‘Western’ diet, enriched with saturated fat and cholesterol. Socially-housed adult female cynomolgus monkeys (n=36) were fed the Western diet for 27 months and depressive behavior was recorded weekly. Body weight, body mass index and circulating cholesterol profiles were measured in all animals, and fatty acids (FA) and FA-based signaling molecules were measured in the 6 least and 6 most depressed monkeys. Monkeys consuming the Western diet exhibited a broad range of percent time spent in depressive behavior. The percent time spent depressed was positively correlated with total plasma and LDL cholesterol and negatively correlated with HDL cholesterol. Despite being leaner, depressed monkeys had higher concentrations of monounsaturated fats (C16:1 and C17:1), a higher ω6/ω3 polyunsaturated fatty acid (PUFA) ratio and higher concentrations of omega-6 (ω6) PUFAs, particularly C18:2ω6 and C20:3ω6. FA ratios suggest that stearoyl CoA desaturase 1 activity was increased in depressed monkeys. Depressed female cynomolgus monkeys had elevated concentrations of serum lipids and lipid signaling molecules that are typically associated with obesity, insulin resistance and cardiovascular disease, which may account in part for the comorbidity of depression and CHD.

Dietary botanical seed oils may influence common diseases associated with systemic inflammation such as asthma and diabetes. We have previously determined the optimal dietary concentrations of two botanical seed oils from borage (Borago officinalis) and echium (Echium plantagineum) necessary to reduce ex vivo leukotriene generation in asthmatic subjects. The current study compared the impact of dietary supplementation with borage/echium and corn (placebo) or fish oil on insulin levels in 59 diabetes/metabolic syndrome subjects. Serum PUFA levels changed as expected based on the dietary oil (corn, botanical or fish) provided to subjects. When examined as a group, there was no statistical difference in insulin levels among the dietary groups. A variant LTC4 synthase genotype (−444 LTC4S or rs730012) has been identified that is associated with high levels of mRNA for LTC4S, leukotrienes and responsiveness to leukotriene blockers The borage/echium oil combination, but not placebo or fish oil, markedly increased insulin levels in individuals with the LTC4S variant. These data suggest that dietary supplementation with borage/echium oils alters insulin levels in diabetic/metabolic syndrome subjects in a genotypic‐specific manner. Supported by NIH PO50AT0027820.