The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets

Hu, Wei; Wei, Ting; Chiang, Wen Dee; Pai, Peiying; Yeh, Yu Lan; Chang, Chung Ho; Lin, Wei‐Ting; Huang, Chih Yang

doi:10.3390/ijms160510158

Cited by 26 publications

(17 citation statements)

References 38 publications

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“…Presently, we have purposed to investigate how effective a potato protein hydrolysate and its derived peptide, a novel compound, can help mitigate NAFLD development in aging model. Following our previous study with a crude protein hydrolysate from potato [6], here we report the results of DIKTNKPVIF peptide synthesized from the original lipolysisactivating PH, highlighting its efficacy to reduce HFD-driven fat deposition and associated proinflammatory response related to NAFLD development in SAMP8 aging mice. Our current model combined two main features: western-like HFD hypernutrition and ageing background.…”

Section: Discussionmentioning

confidence: 99%

“…Hepatosteatosis, the early reversible stage of NAFLD, may progress to nonalcoholic steatohepatitis (NASH) and furtherly to fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [2,3], with subsequent health and social burden [4]. To study fatty liver and potential therapeutic strategy our lab has successfully developed various dietary murine models and investigated protein hydrolysates from soy or potato with beneficial therapeutic effects [5][6][7]. Considering special issues with drug administration in elderly, we purposed in this present work to induce NAFLD in SAMP8 specific strains with HFD and evaluate our natural ingredients.…”

Section: Introductionmentioning

confidence: 99%

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

DUmeUS¹,

Shibu²,

Lin³

et al. 2018

Cell Physiol Biochem

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

DUmeUS¹,

Shibu²,

Lin³

et al. 2018

Cell Physiol Biochem

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“…IGF1R is a direct target of miR‐194 (Han et al, ). It acts through the PI3K‐AKT signaling pathway, affecting the cellular senescence (Hu et al, ). Thus, we speculated whether the presence of miR‐194 might affect cellular senescence.…”

Section: Introductionmentioning

confidence: 99%

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Zhang

Zhu

et al. 2017

Cell Biology International

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MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H O -induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.

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“…In our previous work, alcalase potato protein hydrolysate (APPH) was identified as a cardio‐protective functional food in high‐fat diet animal model and alcalase was reported to hydrolyze some proteins, such as soy into anti‐oxidative hydrolysates . APPH showed to possess lipolysis‐stimulating property, which makes APPH as an efficient anti‐obesity diet ingredient.…”

Section: Introductionmentioning

confidence: 99%

“…APPH showed to possess lipolysis‐stimulating property, which makes APPH as an efficient anti‐obesity diet ingredient. The APPH induced cardiac protection is through the activation of IGF1R‐PI3K‐Akt pathway. High fat diet is known to induce cardiac complications by increased fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Oral administration of alcalase potato protein hydrolysate‐APPH attenuates high fat diet‐induced cardiac complications via TGF‐β/GSN axis in aging rats

Wei

Tamilselvi

et al. 2018

Environmental Toxicology

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Consumption of high fat diet (HFD) is associated with increased cardiovascular risk factors among elderly people. Aging and obesity induced-cardiac remodeling includes hypertrophy and fibrosis. Gelsolin (GSN) induces cardiac hypertrophy and TGF-β, a key cytokine, which induces fibrosis. The relationship between TGF-β and GSN in aging induced cardiac remodeling is still unknown. We evaluated the expressions of TGF-β and GSN in HFD fed 22 months old aging SD rats, followed by the administration of either probucol or alcalase potato protein hydrolysate (APPH). Western blotting and Masson trichrome staining showed that APPH (45 and 75 mg/kg/ day) and probucol (500 mg/kg/day) treatments significantly reduced the aging and HFDinduced hypertrophy and fibrosis. Echocardiograph showed that the performance of the hearts was improved in APPH, and probucol treated HFD aging rats. Serum from all rats was collected and H9c2 cells were cultured with collected serums separately. The GSN dependent hypertrophy was inhibited with an exogenous TGF-β in H9c2 cells cultured in HFD+ APPH treated serum. Thus, we propose that along with its role in cardiac fibrosis, TGF-β also acts as an upstream activator of GSN dependent hypertrophy. Hence, TGF-β in serum could be a promising therapeutic target for cardiac remodeling in aging and/or obese subjects.aging, cardiac hypertrophy, Gelsolin, high fat diet, TGF-β # Wan Teng Lin and Chih Yang Huang contribution equally to this study.

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The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets

Cited by 26 publications

References 38 publications

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

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

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Oral administration of alcalase potato protein hydrolysate‐APPH attenuates high fat diet‐induced cardiac complications via TGF‐β/GSN axis in aging rats

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