Ellagic Acid Alters Muscle Fiber-Type Composition and Promotes Mitochondrial Biogenesis through the AMPK Signaling Pathway in Healthy Pigs

Abstract

Ellagic acid (EA), because of its remarkable health-promoting ability, has aroused widespread interest in the fields of nutrition and medicine. However, no reports showed that EA regulates mitochondrial biogenesis as well as muscle fiber-type composition in pigs. Our study found that dietary 75 and 150 mg/kg EA obviously augmented the slow myosin heavy chain (MyHC) protein level, the number of slow-twitch muscle fibers, and the activity of malate dehydrogenase (MDH) in the longissimus thoracis (LT) muscle of growing-finishing pigs. In contrast, dietary 75 and 150 mg/kg EA decreased the fast MyHC level, the number of fast-twitch muscle fibers, and the activity of lactate dehydrogenase (LDH) in the LT muscle. In addition, our further study found that dietary 75 and 150 mg/kg EA promoted the mitochondrial DNA (mtDNA) content, the mRNA expressions of ATP synthase (ATP5G), mtDNA transcription factor A (TFAM), AMP-activated protein kinase α1 (AMPKα1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and sirtuin 1 (Sirt1), and the level of phospho-LKB1 (P-LKB1), phospho-AMPK (P-AMPK), Sirt1, and PGC-1α in the LT muscle. In vitro, 5, 10, and 20 μmol/L EA treatment upregulated the level of slow MyHC, but only 10 μmol/L EA treatment decreased fast MyHC protein expression in porcine skeletal muscle satellite cells (PSCs). In addition, our data again found that 10 μmol/L EA treatment promoted the mtDNA content, the mRNA levels of ATP5G, mitochondrial transcription factor b1 (TFB1M), citrate synthase (Cs), AMPKα1, PGC-1α, and Sirt1, and the protein expressions of P-AMPK, P-LKB1, PGC-1α, and Sirt1 in PSCs. What is more, inhibition of the AMPK signaling pathway by AMPKα1 siRNA significantly eliminated the improvement of EA on muscle fiber-type composition as well as the mtDNA content in PSCs. In conclusion, EA altered muscle fiber-type composition and promoted mitochondrial biogenesis through the AMPK signaling pathway.

Unsaponifiable matter from walnut oil ameliorate memory deficits and mitochondrial dysfunction in aging mice via activating Nrf2 signaling pathway

“…To ensure proper mitochondrial function, the process of mitochondrial biogenesis plays a crucial role and is by various transcription factors such as NRF-1, PGC-1α, and TFAM that enhance not only the quantity but also the quality of mitochondria. NRF1 is a crucial transcription factor in regulating mitochondrial function and gene expression, while TFAM is an essential DNA-binding protein that controls DNA replication and transcription, as well as participates in mitochondrial fusion and fission [32] . The study found that USM had a significant impact on gene expression, leading to an increase in mitochondrial biogenesis and maintenance of normal cellular function.…”

Ellagic Acid Protects Against Fatigue in Exercise Trained Mice

“…Particularly, the role of EA was widely showed in skeletal muscles. Ingrowing-finishing pigs, EA was involved in regulation of muscle fiber-type composition as represented by augmenting MyHC level and MDH activity 12 . In diabetes-induced muscle atrophy, EA decreased genes expressions related to protein degradation in gastrocnemius 13 .…”

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep

“…As an energy provider, mitochondria are more abundant in oxidized muscle fibers [ 15 ]. Mitochondrial function and number are positively regulated by PGC-1α signaling, and consequently promote oxidative myofibers development [ 16 , 17 ]. Accordingly, enhancing the proportion of oxidative myofibers in skeletal muscle can contribute to improving meat quality and human’s living standards.…”