Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice.

AIMS/HYPOTHESIS: There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity. METHODS: Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota. RESULTS: Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2 ± 12.3, HFHS 153.9 ± 19.3, BBE 114.4 ± 14.3, CLE 82.5 ± 13.0, CRE 152.3 ± 24.4, ABE 90.6 ± 18.0, LGE 95.4 ± 10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l × min]: chow 14.3 ± 1.4, HFHS 31.4 ± 3.1, BBE 27.2 ± 4.0, CLE 17.7 ± 2.2, CRE 32.6 ± 6.3, ABE 22.7 ± 18.0, LGE 23.9 ± 2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice. CONCLUSIONS/INTERPRETATION: Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders. DATA AVAILABILITY: All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).

Body burdens, sources and interrelations of selected toxic and essential elements among the nine Cree First Nations of Eeyou Istchee, James Bay region of northern Quebec, Canada.

BACKGROUND: this article constitutes a report on the comprehensive Nituuchischaayihtitaau Aschii multi-community environment-and-health study conducted among the Cree peoples (Eeyouch) of northern Quebec, Canada. OBJECTIVES: to interpret observed concentrations of a suite of chemical elements in a multi-media biological monitoring study in terms of sources and predictors. METHODS: the concentrations of 5 essential and 6 toxic chemical elements were measured in whole blood, and/or in urine or hair by ICP-MS. Concentrations of essential elements are compared to those considered normal (i.e., required for good health) and, when toxic, deemed acceptable at specified concentrations in public health guidelines. Their dependence on age, sex, the specific community lived-in and diet were explored employing multivariate analysis of variance (MANOVA) involving new variables generated by principle component analysis (PCA) and correspondence analysis (CA). RESULTS: the 5 most prominent PCA axes explained 67.7% of the variation, compared to 93.0% by 6 main CA factors. Concentrations of the essential elements in whole blood (WB) and iodine(i) and arsenic (As) in urine were comparable to those reported in the recent Canadian Health Measures survey and are assigned to dietary sources. By contrast, WB cadmium (Cd) was elevated even when smoking was considered. Mercury (Hg) concentrations in WB and hair were also higher in adults, although comparable to those observed for other indigenous populations living at northern latitudes. Fish consumption was identified as the prominent source. Of the 5 coastal communities, all but one had lower Hg exposures than the four inland communities, presumably reflecting the type of fish consumed. Use of firearms and smoking were correlated with WB-lead (Pb). The concentrations of both Hg and Pb increased with age and were higher in men, while WB-Cd and smoking prevalence were higher in women when considering all communities. Hg and Pb were low in children and women of reproductive age, with few exceedances of health guidelines. Although individuals with T2D had somewhat lower WB-Cd, there is some indication that Cd may potentiate renal dysfunction in this subgroup. Plots of selected CA axes grouped those elements expected to be in a normal diet and distinguished them from those with well-known unique sources (especially Hg and As in hair; and Hg, Pb and Cd in WB). CONCLUSIONS: the use of multiple biological media in conjunction with the complementary PCA and CA approaches for constructing composite variables allowed a more detailed understanding of both the sources of the essential and toxic elements in body fluids and the dependencies of their observed concentrations on age, sex, community and diet.

Omega-3 polyunsaturated fatty acid profiles and relationship with cardiometabolic risk factors in Cree (Eeyouch) of Northern Québec.

BACKGROUND: n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) from fish are known modulators of cardiometabolic risk factors. OBJECTIVE: To examine fatty acids (FAs) status and the relationship between n-3 LC-PUFA and cardiometabolic risk factors in Cree participants. DESIGN: We analyzed data from a cross-sectional study (n=829) conducted in Cree adults (aged 18-74 years) from 7 communities of the James Bay territory of Quebec (Canada) in 2005-2009. Sociodemographic, lifestyle, clinical and anthropometric data were collected. FAs were quantified in red blood cells (RBCs) under fasting conditions. RESULTS: A total of 89% of the participants were overweight (with 69% obesity), 33% had hypertriglyceridemia, 44% had low plasma HDL-c and 77% had fasting plasma insulin ≥90 pmol/l. Total n-3 PUFAs accounted for 6% of total FAs and were higher among older participants, while n-6 PUFAs accounted for 31% of total FAs and were higher among younger participants. According to the adjusted multiple linear regression models, n-3 LC-PUFA was associated (p<0.05) with higher total cholesterol, LDL-c and apo B-100, and was also associated (p<0.05) with lower blood glucose. CONCLUSION: Overall, this study showed that n-3 LC-PUFA levels measured in the RBCs of the Cree adults are relatively low and tend towards lower levels among youth. These levels might be insufficient to offset the prevalence of cardiometabolic risk factors.

Lack of association between fingernail selenium and thyroid cancer risk: a case-control study in French Polynesia.

BACKGROUND: Numerous studies have suggested that selenium deficiency may be associated with an increased risk for several types of cancer, but few have focused on thyroid cancer. MATERIALS AND METHODS: We examined the association between post-diagnostic fingernail selenium levels and differentiated thyroid cancer risk in a French Polynesian matched case-control study. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. RESULTS: The median selenium concentration among controls was 0.76 µg/g. Significantly, we found no association between fingernail selenium levels and thyroid cancer risk after conditioning on year of birth and sex and additionally adjusting for date of birth (highest versus lowest quartile: odds-ratio=1.12, 95% confidence interval: 0.66-1.90; p-trend=0.30). After additional adjustment for other covariates, this association remained non-significant (p-trend=0.60). When restricting the analysis to thyroid cancer of 10 mm or more, selenium in nails was non-significantly positively linked to thyroid cancer risk (p-trend=0.09). Although no significant interaction was evidenced between iodine in nails and selenium in nails effect (p=0.70), a non-significant (p-trend =0.10) positive association between selenium and thyroid cancer risk was seen in patients with less than 3 ppm of iodine in nails. The highest fingernail selenium concentration in French Polynesia was in the Marquises Islands (M=0.87 µg/g) and in the Tuamotu-Gambier Archipelago (M=0.86 µg/g). CONCLUSIONS: Our results do not support, among individuals with sufficient levels of selenium, that greater long-term exposure to selenium may reduce thyroid cancer risk. Because these findings are based on post-diagnostic measures, studies with prediagnostic selenium are needed for corroboration.

Traditional dietary pattern is associated with elevated cholesterol among the Inuit of Nunavik.

Our cross-sectional study assessed the associations between dietary patterns and cardiovascular disease (CVD) risk factors among Nunavik Inuit. This study was conducted as part of the 2004 Nunavik Inuit Health Survey, which included the collection of clinical measurements, plasma samples, and diet information from a food frequency questionnaire. A sample of 666 Inuit aged 18 years and older was included in our analyses. Dietary patterns were generated by principal component analysis. Multivariate general linear models adjusting for sex, age, waist circumference, and other potential confounders were used to examine associations between dietary patterns and CVD risk factors. Four distinct patterns were identified, namely the traditional, Western, nutrient-poor food, and healthy patterns. The traditional pattern showed positive associations with plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B100, LDL peak particle diameter, and oxidized LDL (all P values for trend≤0.04), but showed no association with the total cholesterol:high-density lipoprotein cholesterol ratio or with inflammatory biomarkers (all P values for trend ≥0.19). The nutrient-poor food pattern was positively associated with oxidized LDL (P=0.04), but inversely associated with high-sensitivity C-reactive protein (P<0.0001). The Western and healthy patterns showed no association with any CVD risk factor. Our data show that high adherence to a traditional pattern among Nunavik Inuit is not associated with important changes in CVD risk factors, with the exception of a slight elevation in cholesterol concentrations, most likely attributable to increased n-3 fatty acid intake. Dietary patterns reflecting the recent introduction of market foods in the Inuit diet appear to exert a trivial influence on CVD risk factors.

Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults.

There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (-162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the -108T allele (P=0.009). Our results suggest a gene-environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.

Associations between plasma persistent organic pollutant levels and blood pressure in Inuit adults from Nunavik.

BACKGROUND: Recent evidence suggests that exposure to persistent organic pollutants (POPs) increases the risk of hypertension in environmentally exposed populations. High POP levels have been detected in Arctic populations and the exposure is related to high consumption of fish and marine mammals, which represent the traditional diet of these populations. OBJECTIVE: We examined the associations between polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides and hypertension among Inuit from Nunavik (Quebec, Canada). METHODS: A complete set of data was obtained for 315 Inuit≥18years who participated in the "Santé Québec" health survey that was conducted in the 14 villages of Nunavik in 1992. Fourteen polychlorinated biphenyls (PCBs) and 8 OC pesticides or their metabolites were measured in plasma samples using gas chromatography with electron capture detection. Blood pressure (BP) was measured using a standardized protocol and information regarding anti-hypertensive medication was obtained through questionnaires. The associations between log-transformed POPs and hypertension (systolic BP≥140mmHg, diastolic BP≥90mmHg or anti-hypertensive medication) were analyzed using multiple logistic regressions. RESULTS: Total PCBs as well as the sum of non-dioxin-like PCBs were significantly associated with higher risk of hypertension. Furthermore, the risk of hypertension increased with higher plasma concentrations of congeners 101, 105, 138 and 187. Models adjusted for BP risk factors became significant after including n-3 polyunsaturated fatty acids (PUFAs) and further adjustment for lead and mercury did not change the results. Regarding OC pesticides, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) was associated with increased risk of hypertension while inverse associations were observed with p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), ß-hexachlorocyclohexane (HCH) and oxychlordane. CONCLUSIONS: Some PCB congeners were associated with higher risk of hypertension in this highly exposed population. Most associations became significant after including n-3 PUFAs in the models. However, the analyses of OC pesticides revealed divergent results, which need to be confirmed in further cohort and experimental studies.

Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study.

BACKGROUND: Populations which diet is rich in seafood are highly exposed to contaminants such as mercury, which could affect cardiovascular risk factors OBJECTIVE: To assess the associations between mercury and blood pressure (BP), resting heart rate (HR) and HR variability (HRV) among French Polynesians METHODS: Data were collected among 180 adults (≥ 18 years) and 101 teenagers (12-17 years). HRV was measured using a two-hour ambulatory electrocardiogram (Holter) and BP was measured using a standardized protocol. The association between mercury and HRV and BP parameters was studied using analysis of variance (ANOVA) and analysis of covariance (ANCOVA) RESULTS: Among teenagers, the high frequency (HF) decreased between the 2nd and 3rd tertile (380 vs. 204 ms2, p = 0.03) and a similar pattern was observed for the square root of the mean squared differences of successive R-R intervals (rMSSD) (43 vs. 30 ms, p = 0.005) after adjusting for confounders. In addition, the ratio low/high frequency (LF/HF) increased between the 2nd and 3rd tertile (2.3 vs. 3.0, p = 0.04). Among adults, the standard deviation of R-R intervals (SDNN) tended to decrease between the 1st and 2nd tertile (84 vs. 75 ms, p = 0.069) after adjusting for confounders. Furthermore, diastolic BP tended to increase between the 2nd and 3rd tertile (86 vs. 91 mm Hg, p = 0.09). No significant difference was observed in resting HR or pulse pressure (PP) CONCLUSIONS: Mercury was associated with decreased HRV among French Polynesian teenagers while no significant association was observed with resting HR, BP, or PP among teenagers or adults.

Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik.

BACKGROUND: Methylmercury (MeHg) exposure has been linked to an increased risk of coronary heart disease (CHD). Paraoxonase 1 (PON1), an enzyme located in the high-density-lipoprotein (HDL) fraction of blood lipids, may protect against CHD by metabolizing toxic oxidized lipids associated with low-density liproprotein and HDL. MeHg has been shown to inhibit PON1 activity in vitro, but this effect has not been studied in human populations. OBJECTIVES: This study was conducted to determine whether blood mercury levels are linked to decreased plasma PON1 activities in Inuit people who are highly exposed to MeHg through their seafood-based diet. METHODS: We measured plasma PON1 activity using a fluorogenic substrate and blood concentrations of mercury and selenium by inductively coupled plasma mass spectrometry in 896 Inuit adults. Sociodemographic, anthropometric, clinical, dietary, and lifestyle variables as well as PON1 gene variants (rs705379, rs662, rs854560) were considered as possible confounders or modifiers of the mercury-PON1 relation in multivariate analyses. RESULTS: In a multiple regression model adjusted for age, HDL cholesterol levels, omega-3 fatty acid content of erythrocyte membranes, and PON1 variants, blood mercury concentrations were inversely associated with PON1 activities [ß-coefficient = -0.063; 95% confidence interval (CI), -0.091 to -0.035; p < 0.001], whereas blood selenium concentrations were positively associated with PON1 activities (ß-coefficient = 0.067; 95% CI, 0.045-0.088; p < 0.001). We found no interaction between blood mercury levels and PON1 genotypes. CONCLUSIONS: Our results suggest that MeHg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age.

BACKGROUND: The beneficial effects of prenatal and early postnatal intakes of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. OBJECTIVE: The aim of this study was to examine the relation of n-3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. DESIGN: In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test-Children's Version. RESULTS: Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n-3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA-related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. CONCLUSION: To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n-3 PUFA intake in utero on memory function in school-age children.

Prenatal exposure to methylmercury and PCBs affects distinct stages of information processing: an event-related potential study with Inuit children.

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are seafood contaminants known for their adverse effects on neurodevelopment. This study examines the relation of developmental exposure to these contaminants to information processing assessed with event-related potentials (ERPs) in school-aged Inuit children from Nunavik (Arctic Québec). In a prospective longitudinal study on child development, exposure to contaminants was measured at birth and 11 years of age. An auditory oddball protocol was administered at 11 years to measure ERP components N1 and P3b. Multiple regression analyses were performed to examine the associations of levels of the contaminants to auditory oddball performance (mean reaction time, omission errors and false alarms) and ERP parameters (latency and amplitude) after control for potential confounding variables. A total of 118 children provided useable ERP data. Prenatal MeHg exposure was associated with slower reaction times and fewer false alarms during the oddball task. Analyses of the ERP parameters revealed that prenatal MeHg exposure was related to greater amplitude and delayed latency of the N1 wave in the target condition but not to the P3b component. MeHg effects on the N1 were stronger after control for seafood nutrients. Prenatal PCB exposure was not related to any endpoint for sample as a whole but was associated with a decrease in P3b amplitude in the subgroup of children who had been breast-fed for less than 3 months. Body burdens of MeHg and PCBs at 11 years were not related to any of the behavioural or ERP measures. These data suggest that prenatal MeHg exposure alters attentional mechanisms modulating early processing of sensory information. By contrast, prenatal PCB exposure appears to affect information processing at later stages, when the information is being consciously evaluated. These effects seem to be mitigated in children who are breast-fed for a more extended period.

n-3 Fatty acid intake from marine food products among Quebecers: comparison to worldwide recommendations.

OBJECTIVE: To quantify marine food product consumption and EPA + DHA intake among Quebecers, and to compare the results with the most recent recommendations. DESIGN: Data were obtained from a representative cross-sectional telephone survey (June 2006). Intakes of marine food product species and EPA + DHA were estimated from a validated FFQ on the consumption of marine food products during the previous month. Prevalence of fish oil consumption in the last 6 months was also assessed. SETTING: Province of Quebec (Canada). SUBJECTS: A representative sample (n 1001) of adults in the province of Quebec. Of these, eight were excluded from the present analysis (n 993). RESULTS: Mean and median EPA + DHA intakes for all participants were estimated to be 291 mg/d (sem 11) and 207 mg/d, respectively. 85.0 % (95 % CI 82.7, 87.3) of Quebecers had an EPA + DHA intake lower than 500 mg/d, which is the amount internationally recommended for the prevention of CVD. Mean and median DHA intakes among women of childbearing age (n 128, 18-34 years) were estimated to be 169 mg/d (sem 17) and 126 mg/d, respectively. Of these women, 27.7 % had a daily intake >200 mg DHA and 15.9 % had an intake >300 mg DHA. We noted that 13 % of Quebecers take >or=1 capsule of fish oil/d. CONCLUSIONS: Consumption of marine food products and EPA + DHA among Quebecers clearly appears to be lower than international recommendations. Since EPA + DHA confer health benefits and may reduce health costs, strategies to increase their consumption should be implemented to improve public health in Quebec.

The relation of lead neurotoxicity to the event-related potential P3b component in Inuit children from arctic Québec.

The event-related potential (ERP) P3b, a cognitive electrophysiological measure that has been linked to working memory processing in many experimental paradigms, was measured in Inuit children from Nunavik (Arctic Québec, Canada) to assess lead (Pb) neurotoxicity. Visual and auditory oddball paradigms were administered at 5 (N=27) and 11 (N=110) years of age, respectively, to elicit this ERP component. Pearson correlations and multiple regression analyses were performed to examine the associations between Pb levels and P3b parameters (peak latency and amplitude). Greater prenatal Pb exposure was related to a decrease in P3b amplitude at 5 years of age, and early childhood Pb exposure was associated with delayed P3b latency at 5 years. No significant association was observed at 11 years. These results, in line with those from previous neurobehavioral studies, suggest that Pb exposure affects cognitive processing in children even though the Pb levels measured in a large majority of our sample were below the threshold value for public health intervention used by federal agencies. This study strengthens the arguments for reducing sources of Pb exposure in Nunavik and for lowering the blood Pb concentrations considered "acceptable" in governmental policies.

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.

Decreased activity of desaturase 5 in association with obesity and insulin resistance aggravates declining long-chain n-3 fatty acid status in Cree undergoing dietary transition.

Emerging evidence shows that desaturase 5 (Delta5), the key regulator in the synthesis of highly unsaturated long-chain fatty acids (HUFA), is modulated by factors including adiposity, diet and insulin resistance. We explored the association of these factors in a cross-sectional study within a high-risk Cree population. Anthropometric measures and fasting blood glucose and insulin were analysed. Delta5 was estimated as the 20 : 4n-6:20 : 3n-6 ratio in erythrocyte membranes. The setting of the present study was the Mistissini community in the Cree Territory of Québec, Canada with ninety-eight female and sixty-eight male subjects aged 20-88 years. Obesity (BMI > or = 30 kg/m2) was prevalent across age groups. Delta5 was inversely associated with BMI (Spearman's correlation coefficient (rs) - 0.175; P = 0.03) and positively associated with age (rs 0.593; P < 0.0001), which was driven by age-related increases in dietary intake of n-3 fatty acids and decreases in 20 : 3n-6. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely associated with Delta5 in age-adjusted linear regression analyses in normoglycaemic individuals (beta - 2.110 (SE 0.566); P < 0.001), whereas no association was observed among glucose-intolerant individuals (interaction term P = 0.03). In contrast, there were no significant interactions indicating differences in the slope for each of the adiposity measures in their associations with Delta5. The present study indicates that the dietary transition of reduced consumption of fish among younger Cree may compound the effects of obesity and emerging insulin resistance which, in turn, could reduce bioavailability of HUFA n-3 (through reduced Delta5 activity). Also, the study suggests that disease progression is an important consideration when evaluating correlates of Delta5 activity in observational studies.

Acylation stimulating protein is higher in Inuit from Nunavik compared to a southern Quebec population.

OBJECTIVES: The Inuit of Nunavik in northern Quebec have a lower risk for ischemic heart disease (IHD) compared to Caucasian populations. Acylation stimulating protein (ASP), which is involved in the storage of dietary fat, may play a role. The objective of the study was to determine plasma concentration of ASP in an Inuit and a southern Quebec Caucasian population. STUDY DESIGN: This is a cross-sectional study evaluating the relationship between ASP and dietary factors, such as retinol, whose intake is higher in the Inuit. As well, concentrations of ASP were evaluated in relationship to components of the metabolic syndrome. METHODS: Medical history was collected via a questionnaire and anthropometric measurements and blood samples were collected. RESULTS: ASP was significantly higher in both the Inuit men and women compared to Caucasian men (66.1 +/- 4.1 nM vs 27.5 +/- 2.5 nM, p < 0.0001) and women (71.8 +/- 3.8 nM vs 29.4 +/- 1.3 nM, p < 0.0001). In addition, ASP significantly correlated with total retinol (r = 0.17, p = 0.02) and free retinol (r = 0.15, p = 0.04) in Inuit men but not with other distinctive dietary markers such as omega-3 fatty acids. CONCLUSIONS: Inuit men and women have higher ASP which was unrelated to the number of risk factors for IHD that were present.

High fish consumption in French Polynesia and prenatal exposure to metals and nutrients.

French Polynesians consume high quantities of fish and are therefore exposed to seafood-related contaminants such as mercury (Hg) or lead (Pb) and nutrients such as iodine, selenium and long chain polyunsaturated fatty acids (LC-PUFAs). As the developing foetus is sensitive to contaminants and nutrients, a cross-sectional study was conducted in French Polynesia in 2005-2006 to assess prenatal exposure to contaminants and nutrients through fish consumption. Two hundred and forty one (241) delivering women originating from all islands of French Polynesia were recruited and agreed to answer questions on fish consumption and gave permission to collect umbilical cord blood for metals and nutrients analyses. All parameters were found in high concentrations in cord blood samples except for lead. Mercury concentrations averaged 64.6 nmol/L (or 13 microg/L) with values ranging from 0.25 to 240 nmol/L. Of the sample, 82.5% had Hg concentrations above the US-EPA blood guide-line of 5.8 microg/L. Tuna was the fish species which contributed the most to Hg exposure. High selenium and LC-PUFAs may counterbalance the potential risk of prenatal exposure to Hg in French Polynesia. Due to the high fish consumption of mothers, Polynesian newborns are prenatally exposed to high doses of mercury. Although selenium and omega-3 fatty acids may counteract mercury toxicity, informing pregnant women on both the mercury and nutrient content of local fish species is important.

Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik.

The Inuit are heavily exposed to potentially prooxidant contaminants such as methylmercury (MeHg) and polychlorinated biphenyls (PCB) through their traditional diet. This diet is also an abundant source of n-3 polyunsaturated fatty acids (n-3 PUFA), selenium, and antioxidants, which might reduce cardiovascular risk. Although Inuit from Nunavik have low concentrations of plasma oxidized low-density lipoprotein (OxLDL) and elevated glutathione-related antioxidant defenses, the variance in OxLDL was predicted by PCB and blood glutathione, leaving the issue of contaminant-associated oxidative stress unresolved. The objective of the study was to assess oxidative stress in these Inuit by measuring the plasma concentrations and redox states of alpha-tocopherol and coenzyme Q10 (CoQ10), 2 sensitive biomarkers of oxidative stress, in relation to exposure. Plasma lipophilic antioxidants were determined by high-performance liquid chromatography-coupled electrochemical detection; and their relations to PCB, MeHg, n-3 PUFA, selenium, and OxLDL were assessed by multivariate analyses. Ubiquinol-10, ubiquinone-10, and ubiquinone-10 to CoQ10(total) ratio were elevated as compared with white populations but showed no associations with PCB, MeHg, or n-3 PUFA. Ubiquinol-10 (beta = .23, P = .007) and CoQ10(total) (beta = .27, P = .009) were predicted by blood selenium; and alpha-tocopherol, by PCB (beta = 4.12, P = .0002), n-3 PUFA (beta = 9.16, P = .02), and OxLDL (beta = 3.04, P = .05). Unexpectedly, the alpha-tocopheryl quinone to alpha-tocopherol ratio, in the reference range, was negatively predicted by PCB (beta = -0.41, P = .02). Using sensitive biomarkers of redox alterations, we found no evidence for MeHg- or PCB-associated oxidative stress in these Inuit. However, despite robust blood antioxidant defenses, the unusually elevated ubiquinone-10 to CoQ10(total) ratio (0.21 +/- 0.11) suggests some form of oxidative stress of unknown origin.

Fish consumption and health in French Polynesia.

French Polynesians, like other remote maritime populations are intimately connected to the ocean which nourishes their daily life and culture. Their reliance on fish raises the issue of potential exposure to harmful natural and anthropogenic contaminants as well as providing essential nutrients. The purpose of this study was to assess the risks and benefits of fish consumption in French Polynesia. This cross-sectional study included 195 adults aged 18 years old and over from the Tahiti and Moorea islands. Fatty acids, selenium (Se) and mercury (Hg) blood concentrations were measured in participants and were all very high. Blood concentrations indicate that Hg, Se and omega-3 fatty acids have a common origin, i.e. fish consumption. In comparing the Polynesian group with northern populations, we found that the Polynesian group had levels of Hg similar to those observed in Inuit populations (geometric mean (range): 90.3 (15-420) nmol/L vs. Inuit: m(r): 79.6 (4-560) nmol/L). Similar results were observed with Se blood concentrations. The fatty acid concentration was also similar to that of the Inuit population even though the specific profile of fatty acids differed. For the first time, we report very high blood concentrations of mercury, selenium and omega-3 fatty acids in a fishing population from the South Pacific, comparable to those reported among fishing populations from the Northern hemisphere. Further work is ongoing to better substantiate public health nutritional policies.

Dietary contaminants and oxidative stress in Inuit of Nunavik.

The aim of the present study was to investigate the potential deleterious effects of dietary contaminants such as polychlorinated biphenyls (PCBs) and methylmercury (MeHg) on different molecules sensitive to oxidative stress, namely, plasma oxidized low-density lipoproteins (OxLDLs), plasma homocysteine (Hcy), blood glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). We also planned to assess the potential beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) and selenium (Se) that are also present in the traditional Inuit diet. A total of 99 participants were studied. Plasma levels of PCBs, blood levels of Se and MeHg, plasma lipids (triacylglycerols, total, LDL-, and high-density lipoprotein cholesterol [LDL-C and HDL-C, respectively], apolipoprotein B-LDL), erythrocyte n-3 PUFAs, OxLDL, Hcy, blood GPx, GSH, and GR have been determined. Mean concentrations of MeHg, Se, and PCBs were respectively 10- to 14-fold, 8- to 15-fold, and 16- to 18-fold higher than reported in white population consuming little or no fish. Multivariate analyses show that variance in plasma OxLDL concentrations was predicted by LDL-C (P = .007), HDL-C (P = .005), and PCBs (P = .006). The level of LDL oxidation, represented as the ratio OxLDL/apolipoprotein B-LDL, was predicted by LDL-C (P = .0002), HDL-C (P = .002), and GSH (P = .005). Concentration of plasma Hcy was positively predicted by age (P = .02) but negatively by body mass index (P = .04) and Se (P = .005). Glutathione was predicted by the smoking status (P = .004) and the level of LDL oxidation (P = .005), whereas GR was only predicted by the smoking status (P = .0009). The variance of GPx was not predicted by any contaminant or other physiological parameter. Dietary MeHg showed no association with the examined oxidative biomarkers, whereas PCB level was a predictor of the plasma concentration of OxLDL, although this concentration remained very low. The level of GPx activity in Inuit was higher than levels previously reported to be protective in whites. Homocysteine was negatively predicted by Se, suggesting a possible beneficial effect of Se. Moreover, n-3 PUFAs were highly correlated with dietary contaminants, but had no relationships with oxidative biomarkers. This study suggests that, in adult Inuit, contaminated traditional diet seems to have no direct oxidative effects on molecules involved in oxidative stress.