Hydroxysafflor Yellow A Alters Fuel Selection From Glucose to Fat by Activating the PPARδ Pathway in Myocytes

Abstract

Modulation of fuel selection is critical in skeletal muscle function. Hydroxysafflor yellow A (HSYA) is the major bioactive component in safflower (Carthamus tinctorius L.) and, in our previous study, has been demonstrated to promote a shift from fast to slow myofiber. However, the effects of HSYA on fuel selection in skeletal muscle and its underlying mechanisms remain unclear. In this study, the in vitro experiments found that water extracts of safflower, rich in HSYA, significantly suppressed the expressions of the genes related to glucose utilization and activated the expressions of the lipolysis genes. Furthermore, HSYA resulted in a shift in substrate utilization toward fat relative to carbohydrates in C2C12 myotubes. Animal tests showed HSYA could significantly reduce the respiratory exchange ratio and prolonge endurance performance in mice and also trigger a switch in intramuscular fuel selection preference from carbohydrates to fat at rest and during exercise. Mechanistic studies revealed that HSYA converted this fuel selection by activating peroxisome proliferator activated receptor δ (PPARδ), and these effects of HSYA could be reversed by specific suppression of PPARδ by PPARδ siRNA. Collectively, our study demonstrated that HSYA can switch substrate utilization from glucose to fat in myocytes by activating PPARδ signaling, resulting in prolonged endurance performance. These findings provided direct evidence for the endurance performance enhancement effect of HSYA and explored new perspectives for the innovation and application of HSYA in the health care industry.

Antioxidant and Anti-Inflammatory Properties of Hydroxyl Safflower Yellow a in Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

“…Modern pharmacology and molecular biology studies have verified that HSYA can exert anti-inflammatory, antioxidant ( He et al, 2021 ), and antiischemia reperfusion injury ( Bai et al, 2020 ) effects and is widely used in the treatment of acute or chronic cardiovascular and cerebrovascular diseases ( Xu et al, 2021 ; Geng et al, 2018 ). It has been shown to play a role in ameliorating cognitive impairment ( Zhang et al, 2021a ), rheumatic diseases ( Tsiogkas et al, 2021 ), and osteoporosis ( Wang et al, 2021b ) and regulating glucose and lipid metabolism ( Sun et al, 2021 ), providing new perspectives for exploring the development and application of HSYA in the health care industry ( Sun et al, 2021 ).…”