Abstract
Objectives
To investigate the impact of cyanidin-3-O-glycoside (C3G) and its two major phenolic acid metabolites, protocatechuic acid (PCA) and ferulic acid (FA), on macrophage (MФ) factor-induced inflammation and mitochondrial dysfunction in 3T3-L1 adipocytes.
Methods
Secretory factors from lipopolysaccharide (LPS)-stimulated RAW 274.7 MФ were used to treat adipocytes to simulate the MФ-adipocyte crosstalk in adipose tissue. Alteration of inflammatory responses, including pro-/anti-inflammatory cytokine production and pro-inflammatory signaling pathway activation were evaluated. Mitochondrial respiration, biogenesis and function in MФ factor-induced adipocytes were investigated and the potential role of C3G, PCA and FA was compared. The AMPK-stimulating actions of PCA were explored via determining its impacts on the phosphorylation pattern of key proteins in the AMPK system.
Results
In LPS-conditioned media (CM)-treated adipocytes, C3G, PCA and FA suppressed pro-inflammatory cytokine production (TNF-α: −29.0 to −66.2%; IL-6: −6.6 to −38.2%) and enhanced anti-inflammatory cytokine secretion (adiponectin: 16.1–173.3%) in a dose-dependent manner (P < 0.05). C3G, PCA, and FA down-regulated the expression levels of phosphorylated IκBα and JNK in LPS-CM-stressed adipocytes by 50.5–54.5% and 40.3–56.7% (P < 0.05), respectively. C3G, PCA, and FA alleviated MФ factor-triggered oxidative stress via down-regulating mitochondrial superoxide and mitochondrial dysfunction by up-regulating mitochondrial respiration, in terms of adenosine triphosphate production, oxygen consumption and citrate synthase activity. Compared with C3G and FA, PCA showed better capacity in modulating inflammation and mitochondrial dysregulation in LPS-CM-treated adipocytes (P < 0.05). Further, treatment with PCA increased the AMPK, LKB1, CAMKII, p53, and Akt phosphorylation status while decreased activations in the ACC, mTOR, p70S6k and HSL.
Conclusions
Metabolites of C3G, primarily PCA, alleviated adipogenesis-induced inflammation and mitochondrial alteration in adipocytes, thus having potential implications to prevent adipogenesis-associated disorders.
Funding Sources
USDA-NIFA-HATCH 1,017,440.
The effect of renin–angiotensin system inhibitors on pro‐ and anti‐inflammatory cytokine production
