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

Abstract

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.

TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis

“…Studies show that some natural products can treat agingrelated fibrosis by targeting the TGF-β signalling pathway [151][152][153] (Table 1). Saponins from Panax japonicus (SPJ) exert anti-inflammatory and antioxidative effects.…”

“…After SD rats were fed a high-fat diet for 22 months, the expression of TGF-β and GSN in aging rats was measured; then the rats were treated with APPH, and APPH treatment significantly reduced aging-and high-fat diet-induced hypertrophy and fibrosis. Research indicates that APPH improves high-fat diet-and aging-induced cardiac hypertrophy and fibrosis induced by TGF-β-activated GSN [153]. Metformin is a biguanide, which is a drug class of herbal origin that has been widely used to treat diabetes since the 1950s [154].…”