Protein hydrolysate from potato confers hepatic-protection in hamsters against high fat diet induced apoptosis and fibrosis by suppressing Caspase-3 and MMP2/9 and by enhancing Akt-survival pathway

Shibu Marthandam Asokan,Wan-Teng Lin,Tsu-Han Hung,Wen-Dee Chiang,Zong-Yan Li

doi:10.1186/s12906-019-2700-8

Shibu Marthandam Asokan, Wan-Teng Lin + Show 3 more

Open Access

https://doi.org/10.1186/s12906-019-2700-8

Copy DOI

Abstract

BackgroundA potato protein hydrolysate, APPH is a potential anti-obesity diet ingredient. Since, obesity leads to deterioration of liver function and associated liver diseases, in this study the effect of APPH on high fat diet (HFD) associated liver damages was investigated.MethodsSix week old male hamsters were randomly separated to six groups (n = 8) as control, HFD (HFD fed obese), L-APPH (HFD + 15 mg/kg/day of APPH), M-APPH (HFD + 30 mg/kg/day), H-APPH (HFD + 75 mg/kg/day of APPH) and PB (HFD + 500 mg/kg/day of probucol). HFD fed hamsters were administered with APPH 50 days through oral gavage. The animals were euthanized and the number of apoptotic nuclei in liver tissue was determined by TUNEL staining and the extent of interstitial fibrosis was determined by Masson’s trichrome staining. Modulation in the molecular events associated with apoptosis and fibrosis were elucidated from the western blotting analysis of the total protein extracts.ResultsHamsters fed with high fat diet showed symptoms of liver damage as measured from serum markers like alanine aminotransferase and aspartate aminotransferase levels. However a 50 day long supplementation of APPH effectively ameliorated the effects of HFD. HFD also modulated the expression of survival and apoptosis proteins in the hamster liver. Further the HFD groups showed elevated levels of fibrosis markers in liver. The increase in fibrosis and apoptosis was correlated with the increase in the levels of phosphorylated extracellular signal-regulated kinases (pERK1/2) revealing a potential role of ERK in the HFD mediated liver damage. However APPH treatment reduced the effect of HFD on the apoptosis and fibrosis markers considerably and provided hepato-protection.ConclusionAPPH can therefore be considered as an efficient therapeutic agent to ameliorate high fat diet related liver damages.

Highlights

A potato protein hydrolysate, Alcalase derived potato protein hydrolysate (APPH) is a potential anti-obesity diet ingredient
APPH administration supresses high fat diet (HFD) induced apoptosis and fibrosis Transferase-mediated dUTP Nick End Labeling (TUNEL) staining on liver tissue sections showed increase in the number of TUNEL positive cells in HFD rat groups
Masson’s trichrome staining of liver tissue sections showed that HFD in hamsters triggered hepatic fibrosis which was substantially suppressed in hamsters treated with APPH as seen from the reduction their collagen accumulation (Fig. 2)

Summary

Introduction

Obesity leads to deterioration of liver function and associated liver diseases, in this study the effect of APPH on high fat diet (HFD) associated liver damages was investigated. A high fat diet (HFD) containing high levels of lipids is a major causative factor for hepatic complications like hypercholesterolemia, steatohepatitis, inflammation, apoptosis and fibrosis [6,7,8,9,10]. Liver controls more than 10,000 biochemical reaction at a given time which helps in normal metabolic homeostasis and storage of carbohydrates, lipids, vitamins and minerals [11, 12]. Obesity is one of the most common conditions associated with liver disorders such as liver steatosis, nonalcoholic fatty liver disease and subsequent advancement to steatohepatitis. HFD intake significantly alters the molecular events and function of liver that is reflected with considerable modulation in the functional markers of liver [11]

Methods

Results

Discussion

Conclusion