Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice

Abstract

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.

Effects of diets containing proteins from fish muscles or fish by-products on the circulating cholesterol concentration in rodents: a systematic review and meta-analysis

“…The blood samples for analyses of TC, HDL-cholesterol and LDL-cholesterol were collected at the time of euthanasia for all articles except one, where blood samples were collected 1 week prior to euthanasia (35) . Blood was sampled from fasting rats in the majority of the articles (31,32,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) , while twelve articles declared that animals were not fasted (54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65) . Two articles presented results where half of the rats in each of the experimental groups were non-fasting while the rest of the animals were in a fasting state (66,67) , and four articles did not include information about the prandial state of the animals (35,(68)(69)(70) .…”

“…Most of the included studies were designed with ad libitum access to feed (31,32,34,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)48,50,53,54,56,59,62,63,65,66,68) . The remaining studies were designed with pair feeding (49,64) , slightly restricted access to feed (67) or gave no information on whether feed was freely available or controlled (35,47,51,52,57,58,60,61,69,70) .…”

“…The majority of studies, i.e. thirty-three of the thirty-nine articles included, reported no differences in dietary intake between the intervention and control groups (31,32,34,(36)(37)(38)(39)(40)(41)(42)(43)(44)(47)(48)(49)(51)(52)(53)(54)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)69,70) . The dietary intake was higher in Sprague Dawley rats fed a diet with 100 % of protein from carp muscles (45) and was lower in Wistar rats consuming hydrolysed salmon by-products (55) or hydrolysed muscles or by-products from sardine (46) as the sole protein sources, when compared with rats fed casein diets.…”

A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways

“…The aim of this study was to determine whether the LPH was able to restore the altered lipid profile by the WD; for this motif, the SD group was necessary only to confirm that the WD ingestion induces an alteration of this profile, according to other study designs. 25,[38][39][40][41][42][43] At the end of the experiment, fasted mice were euthanized by an overdose intraperitoneal injection, set for each mouse, of sodium thiopental (50 mg kg −1 , B. Braun Medical SA, Barcelona, Spain) that was effective within 1 min, and the liver was subsequently collected, rapidly frozen, and stored at −80 °C until use. Plasma and hepatic lipid profile parameters were quantified as described in the ESI.…”

An updated review on food‐derived bioactive peptides: Focus on the regulatory requirements, safety, and bioavailability

“…The inhibitory capability remained high throughout GID mimicked in vitro and with the IC 50 value of 3.5 μg/ml. Finally, protamine‐derived peptides RPR (Arg‐Pro‐Arg) were assessed for their antiobesity and hypocholesterolemic effects in high‐fat diet (HFD)‐induced C57BL/6J mice (Mijiti et al., 2021). The findings demonstrated that serum cholesterol concentrations in the protamine and RPR groups were substantially lesser than in the control group.…”