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.

Background & PurposesAging and high‐fat diet (HFD) hypernutrition represent two major risk factors for nonalcoholic fatty liver disease (NAFLD). To investigate the chemopreventive effects of bioactive compounds in fatty liver, our lab has successfully developed various dietary murine models for the past years. Considering special issues with drug administration in elderly subjects, we purposed in this present work to induce NAFLD in senescence‐accelerated mice prone 8 (SAMP8) specific strains with HFD (60% calories from fat) and evaluate a novel bioactive peptide (DIKTNKPVIF) synthesized from a well‐studied lipolysis‐activating potato protein hydrolysate (PH), for its efficacy to reduce HFD‐driven fat deposition and associated proinflammatory events responsible for NAFLD development in SAMP8 aging mice.Methods & ResultsFive groups of six‐month‐old SAMP8 mice (n=4, per group) were submitted to a fourteen‐week experimental study. After sacrifice at ten months of age, liver tissue from individual mouse was collected for histopathological analyses and immunoblot assay. In comparison to the normal chow‐fed control group (NC) with minor aging‐associated hepatic fat depot, HCO group upon the fourteen‐week HFD feeding without treatment displayed widespread hepatic fat droplets evidenced by histopathological analyses of their liver slides. In addition to HFD feeding, a concomitant treatment for the final eight weeks with intraperitoneal dose of the bioactive peptide (HPEP group; 15 mg/kg/d b.w.), oral PH supplementation (HPH group; 50 mg/kg/d b.w.) or oral administration of probucol (HRX group; 500 mg/kg/d b.w) reduced liver steatosis in HPEP, HPH and HRX respectively. Contrary to a very low level of AMPK (HCO vs NC, p<0.001), highly expressed hepatic inflammatory proteins such as p‐38 MAP Kinase, MMP‐9, TNF‐α, IL‐6 were found in HCO. Following the trends of other treatments, the peptide administration reactivated hepatic AMPK (HPEP vs HCO, p<0.05), while significantly downregulated proinflammatory marker p‐p38 and cytokines TNF‐α, FGF‐2.ConclusionsOur set of data show strong evidence for an anti‐steatosis effect of our ten‐amino‐acid peptide (DIKTNKPVIF) and its role to alleviate proinflammatory reaction associated with HFD‐induced hepatosteatosis development in elderly, through activation of AMPK signaling in parallel with the impediment of proinflammatory and mitogenic activities of p‐38 MAPK and FGF‐2. Similarly to PH, our peptide may be suggested as a preventive alternative for NAFLD in elderly subjects.Support or Funding InformationThis work was funded in part by grants from the Ministry of Science and Technology of Taiwan (MOST103‐2410‐H‐029‐037 and MOST104‐2410‐H‐029‐ 033‐MY2). SD (Faculte de Medecine et de Pharmacie, Universite d'Etat d'Haiti ‐ FMP UEH) was financially supported by Taiwan Ministry of Foreign Affairs (MOFA) Scholarship Program for the Republic of Haiti.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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