Dietary Epicatechin Promotes Survival of Obese Diabetic Mice and Drosophila melanogaster

Abstract

The lifespan of diabetic patients is 7-8 y shorter than that of the general population because of hyperglycemia-induced vascular complications and damage to other organs such as the liver and skeletal muscle. Here, we investigated the effects of epicatechin, one of the major flavonoids in cocoa, on health-promoting effects in obese diabetic (db/db) mice (0.25% in drinking water for 15 wk) and Drosophila melanogaster (0.01-8 mmol/L in diet). Dietary intake of epicatechin promoted survival in the diabetic mice (50% mortality in diabetic control group vs. 8.4% in epicatechin group after 15 wk of treatment), whereas blood pressure, blood glucose, food intake, and body weight gain were not significantly altered. Pathological analysis showed that epicatechin administration reduced the degeneration of aortic vessels and blunted fat deposition and hydropic degeneration in the liver caused by diabetes. Epicatechin treatment caused changes in diabetic mice that are associated with a healthier and longer lifespan, including improved skeletal muscle stress output, reduced systematic inflammation markers and serum LDL cholesterol, increased hepatic antioxidant glutathione concentration and total superoxide dismutase activity, decreased circulating insulin-like growth factor-1 (from 303 ± 21 mg/L in the diabetic control group to 189 ± 21 mg/L in the epicatechin-treated group), and improved AMP-activated protein kinase-α activity in the liver and skeletal muscle. Consistently, epicatechin (0.1-8 mmol/L) also promoted survival and increased mean lifespan of Drosophila. Therefore, epicatechin may be a novel food-derived, antiaging compound.

Cocoa and cocoa flavanol epicatechin improve hepatic lipid metabolism in in vivo and in vitro models. Role of PKCζ

“…Similarly, EC restored high TG, NEFA and T-Cho levels in high glucose-challenged HepG2 cells to control values. In line with these results, different cocoa extracts and EC reduced serum and hepatic lipid levels in diabetic rodents (Jalil, Ismail, Chong, Hamidc, & Syed Kamaruddina, 2009;Jalil, Ismail, Pei, Hamid, & Kamaruddin, 2008;Ruzaidi et al, 2005;Si et al, 2011), and grape procyanidins diminished lipid values in HepG2 cells (Guerrero et al, 2013). Moreover, it has also been reported that resveratrol and extracts rich in phenolic compounds from fruits and plants reversed the impaired lipid profile in the liver of diabetic rodents (Im et al, 2014;Kopec, Piatkowska, Leszczynska, & Koronowicz, 2013;Mokiran et al, 2014), as well as in lipidoverloaded hepatic cells .…”

“…Moreover, it has been reported that metabolites derived from a proanthocyanidin-rich extract of cocoa decreased lipid synthesis and excretion in HepG2 cells (Guerrero et al, 2013). Different studies have also demonstrated that cocoa or its main components, such as EC, exert hypoglycaemic and hypolipidaemic effects on several animal models of diabetes and insulin resistance (Cordero-Herrera, Martín, Goya, & Ramos, 2015a;Matsuia et al, 2005;Mokiran et al, 2014;Ramos et al, 2008;Ruzaidi, Amin, Nawalyah, Hamid, & Faizul, 2005;Si et al, 2011). Moreover, cocoa and dark chocolate have been reported to improve insulin sensitivity and lipid profile in healthy humans and T2D patients, alleviating the atherosclerotic cholesterol profile (Baba et al, 2007;Grassi et al, 2008;Mellor, Sathyapalan, Kilpatrick, Beckett, & Atkin, 2010).…”

A literature review of flavonoids and lifespan in model organisms

“…We found ten studies on flavonoids and lifespan studies in D. melanogaster. Three of them used single compounds such as the flavanol epicatechin and the flavonol fisetin (58)(59)(60) , the other seven studies were on cocoa powder, green tea extract, Ludwigia octovalvis extract, apple polyphenols, black tea extract (BTE) and BE (61)(62)(63)(64)(65)(66)(67) (Table 2).…”

Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

“…Epicatechin alone and in combination with exercise has an additive effect to stimulate myocardial angiogenesis (70). Obese, diabetic db/db mice have prolonged lifespan, along with a decrease in markers of inflammation and LDL-cholesterol when treated with epicatechin (79). It is important to note that these animal studies are observational in nature and need to be followed up by more mechanistic studies in the future.…”