Role of extracellular signal-regulated kinase 5 in adipocyte signaling

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Increased adiposity due to energy imbalance is a critical factor of the epidemic crisis of obesity and type II diabetes. In addition to the obvious role in energy storage, regulatory factors are secreted from adipose depots to control appetite and cellular homeostasis. Complex signaling cross-talks within adipocyte are also evident due to the metabolic and immune nature of adipose depots. Here, we uncover a role of extracellular signal-regulated kinase 5 (ERK5) in adipocyte signaling. We find that deletion of ERK5 in adipose depots (adipo-ERK5(-/-)) increases adiposity, in part, due to increased food intake. Dysregulated secretion of adipokines, leptin resistance, and impaired glucose handling are also found in adipo-ERK5(-/-) mice. Mechanistically, we show that ERK5 impinges on transcription factor NFATc4. Decreased phosphorylation at the conserved gate-keeping Ser residues and increased nuclear localization of NFATc4 are found in adipo-ERK5(-/-) mice. We also find attenuated PKA activation in adipo-ERK5(-/-) mice. In response to stimulation of β-adrenergic G-protein-coupled receptor, we find decreased NFATc4 phosphorylation and impaired PKA activation in adipo-ERK5(-/-) mice. Reduced cAMP accumulation and increased phosphodiesterase activity are also found. Together, these results demonstrate integration of ERK5 with NFATc4 nucleo-cytoplasmic shuttling and PKA activation in a

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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