Hélène Jacques

People use dietary supplements to offset nutritional deficiencies and manage metabolic dysfunction. While the beneficial effect of fish proteins on glucose homeostasis is well established, the ability of fish peptides to replicate the protein findings is less clear. With financial support from a programmatic Canadian Institutes of Health Research (CIHR) Team grant, we aimed to identify salmon peptide fractions (SPFs) with the potential to mitigate metabolic dysfunction. Additionally, the grant aims included assessing whether vitamin D, a nutrient commonly found in salmon, could potentiate the beneficial effects of salmon peptides. In parallel, technologies were developed to separate and filter the isolated peptides. We employed an integrative approach that combined nutritional interventions in animal models and human subjects to identify metabolic pathways regulated by salmon peptides and other fish nutrients. This combination of interdisciplinary expertise revealed that a SPF could be a therapeutic tool used in the prevention and management of cardiometabolic diseases. Herein, we present a perspective of our CIHR funded grant that utilized a translational approach to establish the cardiometabolic health effects and mechanisms of action of fish nutrients: from animal models to clinical trials.

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.

Objective This study investigated the effects of a low-dose salmon peptide fraction (SPF) and vitamin D₃ (VitD₃) in obese and VitD₃-deficient mice at risk of metabolic syndrome (MetS). Methods Obese and VitD₃-deficient low-density lipoprotein receptor (LDLr)^−/−/apolipoprotein B100 (ApoB)^100/100 mice were treated with high-fat high-sucrose diets, with 25% of dietary proteins replaced by SPF or a nonfish protein mix (MP). The SPF and MP groups received a VitD₃-deficient diet or a supplementation of 15,000 IU of VitD₃ per kilogram of diet. Glucose homeostasis, atherosclerosis, nonalcoholic fatty liver disease, and gut health were assessed. Results VitD₃ supplementation increased plasma 25-hydroxyvitamin D to optimal status whereas the VitD₃-deficient diet maintained moderate deficiency. SPF-treated groups spent more energy and accumulated less visceral fat in association with an improved adipokine profile. SPF lowered homeostatic model assessment of insulin resistance compared with MP, suggesting that SPF can improve insulin sensitivity. SPF alone blunted hepatic and colonic inflammation, whereas VitD₃ supplementation attenuated ileal inflammation. These effects were associated with changes in gut microbiota such as increased Mogibacterium and Muribaculaceae. Conclusions SPF treatment improves MetS by modulating hepatic and gut inflammation along with gut microbiota, suggesting that SPF operates through a gut-liver axis. VitD₃ supplementation has limited influence on MetS in this model.

Cholecalciferol (D₃) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D₃ are not fully understood. We determined the chronic independent and combined effects of D₃ and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D₃ dose (+SD₃; 1400 IU D₃/kg diet) or a high D₃ dose (+HD₃; 15,000 IU D₃/kg diet). We fed 1 +SD₃ group and 1 +HD₃ group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD₃ differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. D₃ supplementation in the +HD₃ groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D₃ [25(OH)D₃] versus the +SD₃ groups, but it increased 3-epi-25-hydroxyvitamin D₃ levels by 3.4 ng/mL in the HF+ω-6+HD₃ group and 4.0 ng/mL in the HF+ω-3+HD₃ group, representing 30% and 70%, respectively, of the total 25(OH)D₃ increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD₃ group and 7.4% in the HF+ω-3+HD₃ group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD₃ and HF+ω-3+HD₃ groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D₃ supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24–7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D₃ supplementation did not modulate specific taxa. Overall, D₃ supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D–sufficient obese mice.

Exposure to persistent organic pollutants (POPs) is associated with insulin resistance while folic acid (FA) may offer a protective effect. However, the paternal contribution to metabolic phenotypes in offspring is not well known yet. Hence, we investigated whether maternal exposure to POPs affects glucose homeostasis and whether maternal FA supplementation counteracts POP effects transmitted via male descendants. Sprague–Dawley founder dams (F0) were fed a diet containing 2 or 6 mg/kg of FA and were force-fed with either a POP mixture or corn oil for 9 weeks. Subsequent male descendants did not receive any treatment. Blood glucose, plasma insulin and C-peptide were measured during an oral glucose tolerance test in males aged 90 and 180 days from generation 1 (F1), 2 (F2) and 3 (F3). Prenatal POP exposure increased fasting glucose in 90-day-old F1 males and C-peptide in 90-day-old F2 males. Prenatal FA supplementation decreased C-peptide in 90 and 180-day-old F1 males. In 180-day-old F3 males, FA supplementation counteracted POPs on fasting and postglucose C-peptide, indicating reduced insulin secretion. Prenatal exposure to an environmentally relevant POP mixture caused abnormalities in glucose homeostasis that are transmitted from one generation to the next through the paternal lineage. Prenatal FA supplementation counteracted some of the deleterious effects of POPs on glucose homeostasis.

Sea cucumbers have been shown to have potential health benefits and are a rich source of several bioactive compounds, particularly triterpenoid saponins. However, most studies concentrate on the body wall, and little is known about the health effects of the coproducts. The objectives of this study were to determine the nutritional composition of a coproduct from the sea cucumber Cucumaria frondosa and the effects of the dietary consumption of this coproduct on cardiometabolic health in rats. Chemical, biochemical, and nutritional analyses were performed to characterize this coproduct. Forty (40) male Wistar rats were then equally divided into four groups and fed a purified control diet or a diet enriched with 0.5%, 1.5%, or 2.5% (by protein) of coproduct. After 28 days of feeding, the rats were sacrificed. Body and tissue weight, body composition, epididymal adipocyte diameter, plasma and hepatic lipids, glycemia, and insulinemia were measured at the end of the 28-day experiment. Analysis of the coproduct revealed high levels of protein, omega-3 fatty acids, minerals, and saponins. The 1.5% group had significantly smaller epididymal adipocytes vs. the control. We conclude that dietary administration of this sea cucumber coproduct at 1.5% doses decreases visceral adiposity, potentially decreasing the risk of cardiometabolic dysfunction. The coproduct’s saponin content may contribute to the observed effects, but the impact of other components cannot be ruled out.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father’s transmission of environmental effects in addition to mother’s can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/− FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.