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.

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.

• Authors: Geneviève Chevrier, Patricia L Mitchell, Laurie-Eve Rioux, Fida Hasan, Tianyi Jin, Cyril Roland Roblet, Alain Doyen, Geneviève Pilon, Philippe St-Pierre, Charles Lavigne, Laurent Bazinet, Hélène Jacques, Tom Gill, Roger S McLeod, André Marette
• Journal: The Journal of nutrition (J Nutr) Vol. 145 Issue 7 Pg. 1415-22 (Jul 2015) ISSN: 1541-6100 [Electronic] United States
• PMID: 25995281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Society for Nutrition.

Chemical References

• Anti-Inflammatory Agents
• Blood Glucose
• Fish Oils
• Fish Proteins
• Insulin
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• Multiprotein Complexes
• Sucrose
• Mechanistic Target of Rapamycin Complex 1
• Ribosomal Protein S6 Kinases, 90-kDa
• Rps6ka1 protein, mouse
• TOR Serine-Threonine Kinases

Topics

• Adipose Tissue (metabolism)
• Adiposity
• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Blood Glucose (metabolism)
• Body Weight
• Cell Line
• Diet, High-Fat (adverse effects)
• Dyslipidemias (drug therapy)
• Energy Intake
• Fish Oils (administration & dosage)
• Fish Proteins (chemistry, pharmacology)
• Glucose Intolerance (metabolism)
• Inflammation (drug therapy)
• Insulin (blood)
• Insulin Receptor Substrate Proteins (genetics, metabolism)
• Liver (drug effects, metabolism)
• Male
• Mechanistic Target of Rapamycin Complex 1
• Mice
• Mice, Knockout
• Molecular Weight
• Multiprotein Complexes (genetics, metabolism)
• Obesity (drug therapy)
• Ribosomal Protein S6 Kinases, 90-kDa (genetics, metabolism)
• Salmon
• Sucrose (administration & dosage, adverse effects)
• TOR Serine-Threonine Kinases (genetics, metabolism)