adiponectin-activated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by adiponectin binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:mah, GOC:signaling, PMID:20536390]

Adiponectin, a protein hormone primarily produced by adipose tissue, plays a crucial role in regulating metabolic homeostasis. It exerts its effects by activating a signaling pathway involving several key components:

**1. Adiponectin Receptor Binding:** Adiponectin binds to its receptors, AdipoR1 and AdipoR2, which are expressed on various tissues including skeletal muscle, liver, and heart. AdipoR1 is predominantly found in skeletal muscle, while AdipoR2 is more abundant in the liver.

**2. Activation of APPL Proteins:** Upon adiponectin binding, AdipoR1 and AdipoR2 interact with adapter proteins, namely APPL1 (Adiponectin Receptor Protein with Pleckstrin Homology Domain 1) and APPL2, which are essential for downstream signaling.

**3. Activation of AMPK:** AMPK (AMP-activated protein kinase), a key energy sensor in cells, is activated by adiponectin signaling. Adiponectin-mediated activation of AMPK is believed to be mediated by APPL proteins.

**4. Insulin Sensitization:** Adiponectin enhances insulin sensitivity by stimulating glucose uptake and utilization in skeletal muscle and suppressing glucose production in the liver. This effect is primarily attributed to the activation of AMPK, which leads to the phosphorylation and inhibition of key enzymes involved in glucose metabolism.

**5. Fatty Acid Oxidation:** Adiponectin promotes fatty acid oxidation in muscle and liver, contributing to energy expenditure and reducing fat accumulation. This effect is also mediated by AMPK activation.

**6. Anti-Inflammatory Effects:** Adiponectin exhibits anti-inflammatory properties by inhibiting the production of pro-inflammatory cytokines, such as TNF-α and IL-6, in various tissues. This effect is partly mediated by the activation of AMPK, which can suppress inflammatory signaling pathways.

**7. Cardiovascular Protection:** Adiponectin plays a role in cardiovascular protection by improving endothelial function, reducing vascular inflammation, and inhibiting platelet aggregation. These effects are mediated by various mechanisms, including AMPK activation, NO production, and modulation of inflammatory pathways.

**8. Liver Function Regulation:** Adiponectin regulates liver function by promoting insulin sensitivity, reducing hepatic steatosis (fatty liver), and inhibiting inflammation. These effects are largely attributed to the activation of AMPK, which regulates key metabolic pathways in the liver.

**9. Anti-Apoptotic Effects:** Adiponectin exhibits anti-apoptotic effects in various cell types, including cardiomyocytes, hepatocytes, and endothelial cells. This effect may involve the activation of AMPK, which can inhibit apoptotic pathways.

**Overall, adiponectin-activated signaling pathway plays a vital role in regulating metabolic homeostasis, reducing inflammation, and protecting against cardiovascular disease. Its diverse effects are mediated by the activation of AMPK and other downstream signaling molecules, resulting in a complex interplay of cellular responses.**'
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Proteins (3)

Compounds (49)