Bioactive Peptide Improves Diet-Induced Hepatic Fat Deposition and Hepatocyte Proinflammatory Response in SAMP8 Ageing Mice

Abstract

Background/Aims: High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of efficient drug therapy, plant-based bioactive peptides have been studied as alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty liver in aging conditions, researchers highly commended the genetically engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is a paucity of reports about the anti-steatosis effects of bioactive peptides against fatty liver development under a combined action of high-fat diet exposure and aging process. This study was conducted to evaluate the activity of DIKTNKPVIF peptide synthesized from alcalase-generated potato protein hydrolysate (PH), on reducing HFD-driven and steatosis-associated proinflammatory reaction in ageing model. Methods: Five groups of six-month-old SAMP8 mice (n=4, each) were fed either a normal chow (NC group) for 14 weeks upon sacrifice, or induced with a 6-week HFD feeding, then treated without (HCO group) or with an 8-week simultaneous administration of peptide (HPEP group), protein (HPH group) or probucol (HRX group). Liver organs were harvested from each group for histological analysis and immunoblot assay. Results: In contrast to NC, extensive fat accumulation was visualized in the liver slides of HCO. Following the trends of orally administered PH, intraperitoneally injected peptide reduces hepatic fat deposition and causes at protein level, a significant decrease in HFD-induced proinflammatory mediators p-p38 MAPK, FGF-2, TNF-α, IL-6 with concomitant reactivation of AMPK. However, p-Foxo1 and PPAR-α levels were slightly changed. Conclusion: Oral supplementation of PH and intraperitoneal injection of derived bioactive peptide alleviate proinflammatory reaction associated with hepatosteatosis development in elderly subjects, through activation of AMPK.

Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

“…To assess the in vivo effects of the casein-derived peptides, we established the HCD-induced hyperlipidemic mouse model and orally administered peptide 9 or 12 at a concentration of 10 mg/kg to the mice five times a week following the previous study [ 33 ]. Peptide treatment was begun concurrently with HCD administration to investigate both its prophylactic and therapeutic effects.…”

Towards potato protein utilisation: insights into separation, functionality and bioactivity of patatin

“…In addition to the above‐mentioned bioactivities, patatin or patatin‐derived peptides have been reported to show other physiological activities, such as anti‐inflammatory, anticancer, glucose uptake stimulating and neuropeptide inhibitory activities (Sun et al ., ; Fu et al ., ; Dumeus et al ., ). Patatin can display antiproliferative activities towards mouse melanoma B16 cells in a dose‐dependent manner (Sun et al ., ) by inducing cell cycle arrest in the G1 phase and cell apoptosis, which was further verified by flow cytometry.…”

“…A recent study by Dumeus et al . () has reported that a decapeptide (DIKTNKPVIF) from patatin is capable of ameliorating liver steatosis in high fat diet‐fed SAMP8 mice via activating hepatic adenosine 5′‐monophosphate (AMP)‐activated protein kinase signalling and attenuating protein expression of proinflammatory mediators via mitogen‐activated protein kinase signalling pathway.…”

The Potential of Food Protein-Derived Bioactive Peptides against Chronic Intestinal Inflammation

“…After being stimulated, JNK accumulates in the nucleus and causes the corresponding gene (IL-1 and TNF- α ) expression, resulting in inflammatory response ( Figure 2 ) [ 44 ]. Various food protein-derived BAPs can inhibit inflammation via this MAPK pathway, such as DEDTQAMPFR, DEDTQAMPF [ 18 ], FLV [ 20 ], MLGATSL, MSYSAGF [ 18 ], β -Ala-His [ 35 ], pyroGlu-Leu [ 36 ], DIKTNKPVIF [ 45 ], VPP [ 46 ], WH [ 41 ], γ -EC, and γ -EV [ 47 ].…”

“…Numbers of BAPs derived from various food proteins (milk, plant, egg, soybean, meat, wheat, rice, potato, corn silk, fish, etc.) have been found to be well suited to treat inflammation or IBD symptoms in vivo ( Table 2 ), such as Ala-Gln (AQ) [ 9 , 52 – 54 ], DIKTNKPVIF [ 45 ], EWP [ 55 ], GLTSK [ 56 ], glycomacropeptide [ 57 – 60 ], lunasin [ 15 ], IRW [ 11 , 61 – 63 ], IQW [ 62 – 64 ], KGHYAERVG [ 65 ], KPV [ 66 ], PTGADY [ 67 ], QCQCAVEGGL [ 68 ], QEPVL, QEPV [ 6 ], RILSILRHQNLLKELQDLAL [ 69 ], SSEDIKE [ 70 ], TMKLLLVTL [ 43 ], VPP [ 31 , 46 , 71 , 72 ], IPP [ 71 , 72 ], VPY [ 33 ], WH [ 41 ], casein hydrolysates [ 73 ], soybean dipeptides and tripeptides [ 74 ], peptide P-317 [ 75 ], pyroGlu-Leu [ 76 ], β -Casofensin [ 77 ], γ -EC, and γ -EV [ 47 ]. These studies suggest that oral administration of food-derived BAPs have anti-inflammatory effects, and they can be the therapeutic agents for inflammatory-related diseases, including IBD [ 78 ].…”