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Published on: February 12, 2020
Cistanoside F Ameliorates Lipid Accumulation and Enhances Myogenic Differentiation via AMPK-Dependent Signaling in
Meng-Ling Ma1, Ze-Ling Tang1, Li-Ping Chen1
1Department of Biochemistry, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Abstract:
Sarcopenic obesity (SO) is a metabolic disorder for which no effective pharmacological treatments are currently available. Cistanoside F (Cis), a phenoxyethanol-derived compound, remains relatively unexplored in the context of lipid metabolism regulation, as well as its potential mechanisms and therapeutic applications in metabolic disorders. Consequently, this study aimed to evaluate the potential of Cis in ameliorating the pathological manifestations of SO in C2C12 cells. Two classical adipogenic differentiation models using C2C12 cells were employed to quantitatively assess the ability of Cis to inhibit lipid droplet formation, utilizing Oil Red O staining coupled with high-content imaging analysis. Markers associated with adipogenic and myogenic differentiation were examined using quantitative real-time PCR and Western blotting. Our experimental findings demonstrated that Cis significantly attenuated lipid droplet accumulation and promoted muscle protein synthesis via the modulation of PPARγ, ATGL, CPT1b, and UCP1 expression during lipogenic differentiation of C2C12 cells. Cis significantly upregulated the phosphorylation and expression levels of key metabolic regulators, including p-AMPK/AMPK, p-ACC1/ACC1, and MHC. We identified a positive regulatory feedback mechanism between AMPK signaling and MHC expression in the adipogenic differentiation model, suggesting that Cis exerts its therapeutic effects through AMPK-dependent pathways. This is the first study to provide the first experimental evidence supporting the therapeutic potential of Cis for metabolic regulation, targeting adiposity reduction and muscle mass enhancement. Furthermore, Cis exhibited potent anti-inflammatory properties, as demonstrated by its ability to significantly downregulate proinflammatory mediators, including IL-6 and p-NF-κB/NF-κB, during adipogenic differentiation. These novel findings regarding the anti-inflammatory mechanisms of Cis will form the basis for our subsequent in-depth mechanistic investigations.
Insights
Cistanoside F (Cis) shows promise for treating sarcopenic obesity by reducing fat accumulation and boosting muscle growth. This compound also demonstrates anti-inflammatory effects, offering new therapeutic avenues.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Disorders
Background:
- Sarcopenic obesity (SO) is a metabolic disorder lacking effective pharmacological treatments.
- Cistanoside F (Cis), a phenoxyethanol derivative, has unexplored potential in lipid metabolism and metabolic disorders.
Purpose of the Study:
- To evaluate Cistanoside F's efficacy in ameliorating sarcopenic obesity manifestations in C2C12 cells.
- To investigate the underlying mechanisms of Cis in regulating adipogenesis and myogenesis.
Main Methods:
- Utilized C2C12 cell adipogenic differentiation models.
- Quantified lipid droplet accumulation using Oil Red O staining and high-content imaging.
- Assessed gene and protein expression of key metabolic and differentiation markers via qPCR and Western blotting.
Main Results:
- Cis significantly inhibited lipid droplet accumulation and promoted muscle protein synthesis.
- Cis modulated PPARγ, ATGL, CPT1b, and UCP1 expression during lipogenic differentiation.
- Cis upregulated p-AMPK/AMPK, p-ACC1/ACC1, and MHC, indicating AMPK pathway activation.
- Cis demonstrated anti-inflammatory effects by downregulating IL-6 and p-NF-κB/NF-κB.
Conclusions:
- Cistanoside F exhibits therapeutic potential for sarcopenic obesity by reducing adiposity and enhancing muscle mass.
- Cis acts through AMPK-dependent pathways, establishing a feedback loop with MHC expression.
- Cis possesses significant anti-inflammatory properties, suggesting broader therapeutic applications.
