Animal and Cellular Studies Demonstrate Some of the Beneficial Impacts of Herring Milt Hydrolysates on Obesity-Induced Glucose Intolerance and Inflammation

Abstract

The search for bioactive compounds from enzymatic hydrolysates has increased in the last few decades. Fish by-products have been shown to be rich in these valuable molecules; for instance, herring milt is a complex matrix composed of lipids, nucleotides, minerals, and proteins. However, limited information is available on the potential health benefits of this by-product. In this context, three industrial products containing herring milt hydrolysate (HMH) were tested in both animal and cellular models to measure their effects on obesity-related metabolic disorders. Male C57Bl/6J mice were fed either a control chow diet or a high-fat high-sucrose (HFHS) diet for 8 weeks and received either the vehicle (water) or one of the three HMH products (HMH1, HMH2, and HMH3) at a dose of 208.8 mg/kg (representing 1 g/day for a human) by daily oral gavage. The impact of HMH treatments on insulin and glucose tolerance, lipid homeostasis, liver gene expression, and the gut microbiota profile was studied. In parallel, the effects of HMH on glucose uptake and inflammation were studied in L6 myocytes and J774 macrophages, respectively. In vivo, daily treatment with HMH2 and HMH3 improved early time point glycemia during the oral glucose tolerance test (OGTT) induced by the HFHS diet, without changes in weight gain and insulin secretion. Interestingly, we also observed that HMH2 consumption partially prevented a lower abundance of Lactobacillus species in the gut microbiota of HFHS diet-fed animals. In addition to this, modulations of gene expression in the liver, such as the upregulation of sucrose nonfermenting AMPK-related kinase (SNARK), were reported for the first time in mice treated with HMH products. While HMH2 and HMH3 inhibited inducible nitric oxide synthase (iNOS) induction in J774 macrophages, glucose uptake was not modified in L6 muscle cells. These results indicate that milt herring hydrolysates reduce some metabolic and inflammatory alterations in cellular and animal models, suggesting a possible novel marine ingredient to help fight against obesity-related immunometabolic disorders.

Herring Milt and Herring Milt Protein Hydrolysate Are Equally Effective in Improving Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese- and Insulin-Resistant Mice

“…The discrepancy might be a result of differences in the administration route, dose and composition of the test materials between the two studies. In our study, the entire herring milt was directly dried up or pretreated with enzymatic hydrolysis of proteins prior to dry up, whereas the study by Durand et al used herring milt protein hydrolysate extracts that contained different protein, lipid, nuclei acid, and astaxanthin contents [ 22 ]. The dose of the test materials in the study by Durand et al was 208.8 mg/kg by daily gavage, which was around 60-fold lower than the dose provided through diet in the present study.…”

“…A mouse study showed that dietary supplementation of herring milt tended to lower the plasma level of several pro-inflammatory cytokines [ 20 ]. Several in vivo and in vitro studies have shown that proteins, protein hydrolysates, or peptides of sardine, salmon, and tuna lower pro-inflammatory cytokine release, inflammatory cell count [ 13 , 45 , 46 , 47 ], and the production of inflammatory mediator iNOS [ 22 ]. The anti-inflammatory benefits of herring milt and fish proteins/hydrolysates may be related at least in part to their high contents of omega-3 EPA and DHA, which are well-established for the anti-inflammatory properties [ 20 , 30 ].…”

“…The balance between growth hormone and insulin-like growth factor-1 determines insulin secretion and sensitivity [ 55 ]. Moreover, l -arginine induces the activation of the mitogen-activated protein kinase (MAPK), AMPK [ 22 , 34 , 56 ], and sucrose nonfermenting AMPK-related kinase (SNARK) [ 22 ], which play important roles in the physiological adjustment of insulin singling and sensitivity and the subsequent maintenance of circulating glucose at appropriate levels [ 57 ]. Indeed, a study in high-fat diet-induced obese rats demonstrated that dietary supplementation of cod protein improved insulin signaling by restoring the insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4-translocaton [ 9 ].…”

Genomics and Personalized Nutrition

“…The purpose of this Special Issue was to expand and add to the research which uses genomics technologies in the development of personalized nutrition recommendations. This Special Issue on “Genomics and Personalized Nutrition” features five original articles [ 5 , 6 , 7 , 8 , 9 ] and four reviews [ 10 , 11 , 12 , 13 ] which examine two facets of personalized nutrition: 1—genomics and food bioactive compounds; and 2—genetic variations and diet interactions.…”

“…Two articles in this Special Issue establish the impact of food bioactive compounds on several genomic parameters, such as gene expression and microbiome, to understand the effects on metabolic syndrome. First, Durand et al, 2020 [ 5 ] demonstrate that a supplement of milt herring hydrolysates improves glycemia, reduces inflammation, modulates gene expression in the liver, and alters Lactobacillus abundance. Overall, this study suggests that milt herring is a novel marine ingredient to help fight against metabolic syndrome.…”