5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3–Adenosine Monophosphate-Activated Protein Kinase Pathway

Abstract

5-Heptadecylresorcinol (AR-C17), a well-known biomarker for whole grain rye consumption, is a primary homolog of alkylresorcinols. In this study, the effects of AR-C17 on the thermogenesis of brown adipocytes and 3T3-L1 adipocytes were investigated. The results showed that AR-C17 increased sirtuin 3 (Sirt3) expression, and the expressions of specific thermogenic genes in adipocytes were increased. Furthermore, AR-C17 increased the mitochondrial functions during the thermogenic activation of adipocytes. In in vivo study, AR-C17 increased the cold tolerance and thermogenic capacity of adipose tissues in aging mice. In addition, Sirt3 activity was required for AR-C17-induced thermogenesis. Meanwhile, AR-C17 increased adenosine monophosphateactivated protein kinase (AMPK) phosphorylation, and AMPK was involved in the regulation of AR-C17 on thermogenic adipocytes. Mechanically, AR-C17 upregulated a Sirt3−AMPK positive-feedback loop in adipocytes and further increased the expression of uncoupling protein 1 to activate thermogenesis. This study indicated that AR-C17 could be a promising thermogenic activator of adipocytes to alleviate obesity and aging-associated metabolic diseases.

5-Heptadecylresorcinol Improves Aging-Associated Hepatic Fatty Acid Oxidation Dysfunction via Regulating Adipose Sirtuin 3

“…Sirt3 plays a crucial role in the regulation of energy metabolism and can regulate many metabolic processes, such as oxidative phosphorylation, FA oxidation, and the tricarboxylic acid cycle [25]. In our previous study, we showed that AR-C17 improved the metabolism of thermogenic fat and the thermogenic capacity of aged mice via the regulation of Sirt3 [22]. Furthermore, we also revealed that AR-C17 improved the BAT thermogenesis of aged mice via enhancing the acylcarnitine metabolism of BAT [26].…”

“…5-Heptadecylresorcinol (AR-C17) is a major active homolog of ARs and has been demonstrated to have various health benefits, including anti-oxidant, anti-obesity, anti-inflammatory, and anti-cancer activities [16][17][18][19]. AR-C17 has been demonstrated to modulate various metabolic processes via regulating Sirtuin 3 (Sirt3) [16,[20][21][22]. Sirt3 is a human Sir2 homologue which translocates into mitochondria under cellular stress [23].…”

Quercetin Enhances the Availability of 5-Heptadecylresorcinol by Inhibiting the Expression of P-gp

“…All mice were given one-time oral gavage. The dosage of intragastric administration in mice is based on Zhang et al, 13 in which the dosage of AR-C17 in mice was 250 μg/ kg/day, n = 6. Besides, note that the concentration ratio mentioned above means "Quercetin: AR-C17".…”

“…It has been reported that AR-C17 can improve cognitive impairment and relieve neuroinflammation in mice . Besides, our previous study demonstrated that AR-C17 is a promising thermogenic activator for adipocytes to relieve metabolic diseases related to obesity and aging . Therefore, AR-C17 has significant potential that deserves further nutrition development.…”

“…12 Besides, our previous study demonstrated that AR-C17 is a promising thermogenic activator for adipocytes to relieve metabolic diseases related to obesity and aging. 13 Therefore, AR-C17 has significant potential that deserves further nutrition development. Although plenty of studies have demonstrated that AR-C17 provides incalculable benefits for human health, its poor bioavailability limits the maximization of its functional benefits.…”