Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood lipid levels

Consumption of long-chain n-3 PUFA, particularly DHA, has been shown to improve cardiovascular risk factors but the intake required to achieve benefits is unclear. We sought to determine the relationship between DHA intake, increases in erythrocyte DHA content and changes in blood lipids. A total of sixty-seven subjects (thirty-six male, thirty-one female, mean age 53 years) with fasting serum TAG ≥ 1·1 mmol/l and BMI>25 kg/m² completed a 12-week, randomized, double-blind, placebo-controlled parallel intervention. Subjects consumed 2, 4 or 6 g/d of DHA-rich fish oil (26 % DHA, 6 % EPA) or a placebo (Sunola oil). Fasting blood lipid concentrations and fatty acid profiles in erythrocyte membranes were assessed at baseline and after 6 and 12 weeks. For every 1 g/d increase in DHA intake, there was a 23 % reduction in TAG (mean baseline concentration 1·9 (sem 0·1) mmol/l), 4·4 % increase in HDL-cholesterol and 7·1 % increase in LDL-cholesterol. Erythrocyte DHA content increased in proportion to the dose of DHA consumed (r 0·72, P < 0·001) and the increase after 12 weeks was linearly related to reductions in TAG (r − 0·38, P < 0·01) and increases in total cholesterol (r 0·39, P < 0·01), LDL-cholesterol (r 0·33, P < 0·01) and HDL-cholesterol (r 0·30, P = 0·02). The close association between incorporation of DHA in erythrocytes and its effects on serum lipids highlights the importance of erythrocyte DHA as an indicator of cardiovascular health status.

A global approach to dissecting lipid-induced impairment of liver gluconeogenesis

This thesis identified: 1) novel aspects of cholesterol metabolism, 2) a novel signalling lipid in the phosphatidylinositol class, and 3) a gene involved in regulating lipid breakdown, as being regulated in the reversal of a fatty acid induced diabetic liver. The identification of these targets may allow for future development of targeted therapies against type 2 diabetes with a specific focus on the liver.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.

Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.

n-3 LC-PUFA deposition efficiency and appetite regulating hormones are modulated by the dietary lipid source during rainbow trout grow-out and finishing periods

Largely attributable to concerns surrounding sustainability, the utilisation of omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in aquafeeds for farmed fish species is an increasingly concerning issue. Therefore, strategies to maximise the deposition efficiency of these key health beneficial fatty acids are being investigated. The present study examined the effects of four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma concentrations of the appetite-regulating hormones, leptin and ghrelin, during the grow-out and finishing phases in rainbow trout culture. Minimal detrimental effects were noted in fish performance; however, major modifications were apparent in tissue fatty acid compositions, which generally reflected that of the diet. These modifications diminished somewhat following the fish oil finishing phase, but longer-lasting effects remained evident. The fatty acid composition of the alternative oils was demonstrated to have a modulatory effect on the deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved in appetite regulation, growth and feed intake during both the grow-out and finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to ‘spare’ the catabolism of n-3 LC-PUFA and, as such, resulted in the highest retention of these fatty acids, ultimately highlighting new nutritional approaches to maximise the maintenance of the qualitative benefits of fish oils when they are used in feeds for aquaculture species.