Pierre Julien

Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes.

BACKGROUND Polyunsaturated fatty acids (PUFAs) are intrinsic cell membrane components and closely involved in neurotransmission and receptor function. Lower omega-3 levels are associated with increased risk of coronary artery disease (CAD), increases in cardiac events in CAD patients, and depression. We sought to examine relationships between depression and serum levels of omega-3 and omega-6 PUFAs in patients recovering from acute coronary syndromes (ACS). METHODS We carried out a case-control study of serum PUFA levels and current major depression in 54 age- and sex-matched pairs approximately 2 months following ACS. RESULTS Depressed patients had significantly lower concentrations of total omega-3 and docosahexaenoic acid (DHA), and higher ratios of arachidonic acid (AA) to DHA, AA to eicosapentaenoic acid (EPA), and n-3 to n-6 than controls. There were no baseline differences in any potential risk or protective factors for depression. CONCLUSIONS Results are consistent with previous reports in depressed patients without CAD, and with literature concerning omega-3 levels and risk of CAD events. Dietary, genetic, and hormonal factors may all play a role in both depression and CAD. Both prospective studies and randomized trials are needed to help clarify the interrelationships.

High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model

To investigate potential dietary risk factors of Alzheimers disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.

Molecular pathobiology of the human lipoprotein lipase gene

Lipoprotein lipase (LPL; E.C. 3.1.1.34) is a key enzyme in the metabolism of lipids. Many diseases, including obesity, coronary heart disease, chylomicronemia (pancreatitis), and atherosclerosis, appear to be directly or indirectly related to abnormalities in LPL function. Human LPL is a member of a superfamily of lipases that includes hepatic lipase and pancreatic lipase. These lipases are characterized by extensive homology, both at the level of the gene and the mature protein, suggesting that they have a common evolutionary origin. A large number of natural mutations have been discovered in the human LPL gene, which are located at different sites in the gene and affect different functions of the mature protein. There is a high prevalence of two of these mutations (207 and 188) in the Province of Québec, and one of them (207) is almost exclusive to the French-Canadian population. A study of these and other naturally occurring mutant LPL molecules, as well as those created in vitro by site-directed mutagenesis, indicate that the sequence of LPL is organized into multiple structural and functional units that act in concert in the normal enzyme. In this review, we discuss the interrelationships of LPL structure and its function, the molecular etiology of abnormal LPL in humans, and the clinical and therapeutic aspects of LPL deficiency.

Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging

BACKGROUND Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against dementia, although epidemiologic studies have yielded inconclusive results. Fish is the main dietary source of n-3 PUFAs and is sometimes contaminated with mercury. This neurotoxicant may modify the association with dementia. OBJECTIVE We evaluated the association of erythrocyte membrane total n-3 PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and blood mercury with the incidence of dementia and Alzheimer disease (AD) in the Canadian Study of Health and Aging (CSHA) with adjustment for confounders including apolipoprotein E epsilon4 (APOE epsilon4) status. DESIGN The CSHA is a cohort study of a representative sample of persons aged > or =65 y, conducted from 1991 to 2002. A subsample of 663 nondemented CSHA subjects with a complete clinical examination, blood samples, and follow-up information was eligible for prospective analyses on laboratory measurements. Of these, 149 were incident cases of dementia, including 105 with AD. RESULTS In adjusted Cox regression models with age as the time scale, there were no associations between total n-3 PUFAs, DHA, or EPA and dementia or AD. In contrast, a mercury concentration in the highest quartile was associated with a reduced risk of dementia (hazard ratio: 0.53; 95% CI: 0.33, 0.88). However, significant risk reductions were limited to subjects with concentrations of both n-3 PUFAs and mercury that were above the median. There was no modification of risk by APOE epsilon4 status. CONCLUSIONS No associations between n-3 PUFAs and dementia or AD were found. The results regarding mercury may indicate a spurious association.

Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long‐chain omega‐3 polyunsaturated fatty acids (LCn–3PUFA) from fish oil are known to improve insulin‐mediated glucose metabolism in insulin‐resistant states, their potential role in regulating insulin‐mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LCn–3PUFA‐rich menhaden oil with an iso‐energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LCn–3PUFA potentiate insulin action by increasing the insulin‐stimulated whole‐body disposal of amino acids from 152 to 308 μmol kg−1 h−1 (P= 0.006). The study further showed that in the fed steady‐state, chronic adaptation to LCn–3PUFA induces greater activation (P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole‐body total flux of phenylalanine was reduced from 87 to 67 μmol kg−1 h−1 (P= 0.04) and oxidative metabolism was decreased (P= 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin‐sensitive aspects of protein metabolism.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

Fatty acid composition of wild and farmed Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss).

The goal of this study was to examine the FA composition of wild and farmed Atlantic salmon (AS) and rainbow trout (RT). FA profiles were obtained by GC/FID. Results showed that lipid and n−3 highly unsaturated FA contents of farmed and wild AS were similar. Total n−3 and n−6 PUFA were significantly higher in farmed AS than in wild AS. Farmed RT contained more fat and less n−3 PUFA than wild RT. Our results show that farmed salmonids provide high levels of n−3 HUFA to consumers.

Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia

Please cite this paper as: Dr Wei SQ, Audibert F, Hidiroglou N, Sarafin K, Julien P, Wu Y, Luo ZC, Fraser WD. Longitudinal vitamin D status in pregnancy and the risk of pre‐eclampsia. BJOG 2012;119:832–839.

A Mutation in the Human Lipoprotein Lipase Gene as the Most Common Cause of Familial Chylomicronemia in French Canadians

BACKGROUND Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population. METHODS The entire coding sequence of the lipoprotein lipase gene from one French Canadian patient was amplified by the polymerase chain reaction and sequenced. Exon 5 from 36 other French Canadian patients was amplified and analyzed by dot blot hybridization with allele-specific oligonucleotides. RESULTS Sequence analysis revealed a missense substitution of leucine (CTG) for proline (CCG) at residue 207 in exon 5. This mutation was found on 54 of the 74 mutant alleles (73 percent) in the patients. Studies of site-directed in vitro mutagenesis have confirmed that this mutation generates inactive lipoprotein lipase and is the cause of lipoprotein lipase deficiency. CONCLUSIONS We have identified a missense mutation at residue 207 of the lipoprotein lipase gene that is the most common cause of lipoprotein lipase deficiency in French Canadians. This mutation can be easily detected by dot blot analysis, providing opportunity for definitive DNA diagnosis of the disorder and identification of heterozygous carriers.

Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys

Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0 .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (P < 0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism.