Salmon peptides limit obesity-associated metabolic disorders by modulating a gut-liver axis in vitamin D-deficient mice.

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.

Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.

BACKGROUND: We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects. OBJECTIVES: We tested whether a salmon peptide fraction (SPF) could improve MetS in mice and explored potential mechanisms of action. METHODS: ApoB(100) only, LDL receptor knockout male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1 group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We assessed the impact of dietary treatments on glucose tolerance, adipose tissue inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide synthase activity were further studied in vitro with the use of L6 myocytes, FAO hepatocytes, and J774 macrophages. RESULTS: Mice fed HFS+SPF or HFS+SPF+FO diets had lower body weight (protein effect, P = 0.024), feed efficiency (protein effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower concentrations of adipose tissue cytokines and chemokines (protein effect, P ≤ 0.003) compared with HFS and HFS+FO groups. They also had greater glucose tolerance (protein effect, P < 0.001), lower activation of the mammalian target of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1 (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002) than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS activation in vitro. CONCLUSIONS: SPF reduces obesity-linked MetS features in LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory properties of SPF were confirmed in L6 myocytes, FAO hepatocytes, and J774 macrophages.

Crucial roles of charged saccharide moieties in survival of gram negative bacteria against protamine revealed by combination of grazing incidence x-ray structural characterizations and Monte Carlo simulations.

Grazing incidence x-ray scattering techniques and Monte Carlo (MC) simulations are combined to reveal the influence of molecular structure (genetic mutation) and divalent cations on the survival of gram negative bacteria against cationic peptides such as protamine. The former yields detailed structures of bacterial lipopolysaccharide (LPS) membranes with minimized radiation damages, while the minimal computer model based on the linearized Poisson-Boltzmann theory allows for the simulation of conformational changes of macromolecules (LPSs and peptides) that occur in the time scale of ms. The complementary combination of the structural characterizations and MC simulation demonstrates that the condensations of divalent ions (Ca2+ or Mg2+) in the negatively charged core saccharides are crucial for bacterial survival.