Phosphorylation by the mitogen-activated protein kinases (ERK- and p38-MAPK), Protein Kinase A and C (PKA, PKC), AMP Kinase (AMPK) and glycogen synthase kinase-3 (GSK3) affect their activity in a ligand-dependent or -independent manner.

Taken together, our study revealed that OPG signaling promotes liver steatosis through the ERK-PPAR-γ-CD36 pathway. The downregulation of OPG in NAFLD might be a compensatory response of the body to dampen excess hepatic fat accumulation in obesity.

PPAR γ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPAR γ plays an important role in regulating lipid, metabolism in mature adipocytes by …

Jan 15, 2015 · Here we show that ERK directly phosphorylates serine 273 of PPARγ in a robust manner and that Cdk5 suppresses ERKs through direct action on a novel site in MAP kinase/ERK kinase (MEK). Importantly, pharmacological inhibition of MEK and ERK markedly improves insulin resistance in both obese wild-type and ob/ob mice, and also completely reverses ...

Nov 1, 2010 · Posttranslational modifications regulate the function of PPARγ, potentially affecting inflammation. PPARγ contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARγ.

Inhibition of ERK using MEK inhibitor decreased lipid contents in primary hepatocytes from a genetic model of constitutive HIF activation and primary hepatocytes loaded with free fatty acids. Moreover, MEK-ERK inhibition potentiated ligand-dependent activation of PPARα.

Jul 10, 2019 · In the current study, we identified OPG as a secretory protein involved in the regulation of hepatic lipid metabolism in the ERK–PPAR-γ–CD36–dependent pathway and further confirmed the roles of OPG in hepatic steatosis in both in vitro and in vivo studies.

Jan 1, 2021 · We demonstrate that HIF2α-mediated activation of extracellular signal-regulated kinase (ERK) decreases PPARα activity. Inhibition of ERK decreases lipid content in primary hepatocytes via potentiation of PPARα activation and attenuates diet-induced hepatic steatosis.

Mar 3, 2014 · Coimmunoprecipitation of hippocampal extracts revealed that PPARγ and activated, phosphorylated ERK (pERK) associated in Tg2576 in vivo, and that PPARγ agonism facilitated recruitment of PPARγ to pERK during memory consolidation.

Feb 14, 2005 · Our recent studies have demonstrated a role for MEK/ERK signaling and CCAAT/enhancer binding proteins (C/EBP)β in regulating expression of PPARγ during adipogenesis.