title: Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.
abstract: BACKGROUND
  We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chevrier
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Mitchell
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Laurie-Eve
authors.initials: LE
authors.lastname: Rioux
authors.affiliation: Departments of Process Engineering and Applied Science and.
authors.forename: Fida
authors.initials: F
authors.lastname: Hasan
authors.affiliation: Departments of Process Engineering and Applied Science and.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Jin
authors.affiliation: Institute of Nutrition and Functional Foods, and Department of Food Sciences, Laval University, Quebec City, Canada; and.
authors.forename: Cyril Roland
authors.initials: CR
authors.lastname: Roblet
authors.affiliation: Institute of Nutrition and Functional Foods, and Department of Food Sciences, Laval University, Quebec City, Canada; and.
authors.forename: Alain
authors.initials: A
authors.lastname: Doyen
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pilon
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Philippe
authors.initials: P
authors.lastname: St-Pierre
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.
authors.forename: Charles
authors.initials: C
authors.lastname: Lavigne
authors.affiliation: Institute of Nutrition and Functional Foods, and Department of Food Sciences, Laval University, Quebec City, Canada; and.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bazinet
authors.affiliation: Institute of Nutrition and Functional Foods, and Department of Food Sciences, Laval University, Quebec City, Canada; and.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jacques
authors.affiliation: Departments of Process Engineering and Applied Science and.
authors.forename: Tom
authors.initials: T
authors.lastname: Gill
authors.affiliation: Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McLeod
authors.affiliation: Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and andre.marette@criucpq.ulaval.ca.
authors.forename: André
authors.initials: A
authors.lastname: Marette
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D050171:Dyslipidemias / Q000188:drug therapy*; D002149:Energy Intake; D005395:Fish Oils / Q000008:administration & dosage; D029941:Fish Proteins / Q000737:chemistry / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D012474:Salmon; D013395:Sucrose / Q000008:administration & dosage / Q000009:adverse effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D005395:Fish Oils; D029941:Fish Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D046912:Multiprotein Complexes; D013395:Sucrose; D000076222:Mechanistic Target of Rapamycin Complex 1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: amino acids; anti-inflammatory; glucose metabolism; insulin signaling; low-molecular-weight peptide; metabolic syndrome; omega-3 fatty acids; protein hydrolysate