negative regulation of skeletal muscle hypertrophy

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of skeletal muscle hypertrophy. [GO_REF:0000058, GOC:TermGenie, PMID:23470307]

Negative regulation of skeletal muscle hypertrophy is a complex process that involves a variety of signaling pathways and molecular mechanisms. These pathways act to limit the growth of muscle fibers in response to stimuli such as exercise or growth factors. This regulation is crucial for maintaining muscle homeostasis and preventing excessive growth that could lead to muscle damage or dysfunction. Here are some key aspects of this process:

**1. Myostatin Signaling:**
- Myostatin is a potent negative regulator of muscle growth. It binds to its receptor, ActRIIB, on muscle cells, triggering a signaling cascade that inhibits muscle protein synthesis and promotes muscle protein breakdown.
- Myostatin inhibition or knockout leads to increased muscle mass, highlighting its significant role in limiting muscle hypertrophy.

**2. Insulin-like Growth Factor (IGF)-1 and mTOR Pathway:**
- IGF-1 is a key anabolic factor promoting muscle growth. However, its effects are counteracted by negative regulators.
- Negative regulation can occur at multiple levels:
- Reduced IGF-1 production: Stress conditions or aging can lead to reduced IGF-1 production.
- Inhibition of IGF-1 signaling: Certain proteins like IGF-binding proteins (IGFBPs) bind to IGF-1, inhibiting its interaction with its receptor and reducing its signaling activity.
- Suppression of the mTOR pathway: The mTOR pathway, crucial for protein synthesis, can be suppressed by negative regulators. Proteins like TSC1/TSC2 (tuberous sclerosis complex) and AMPK (AMP-activated protein kinase) can inhibit mTOR, dampening muscle growth.

**3. Other Signaling Pathways:**
- **MAPK (mitogen-activated protein kinase) pathways**: The p38 MAPK pathway can negatively regulate muscle hypertrophy by inhibiting protein synthesis and promoting protein degradation.
- **NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway**: Chronic inflammation can activate NF-κB, leading to muscle atrophy and inhibiting hypertrophy.

**4. MicroRNAs (miRNAs):**
- miRNAs are small non-coding RNAs that regulate gene expression.
- Certain miRNAs, such as miR-23a and miR-27b, target mRNAs involved in muscle hypertrophy, leading to their degradation and reduced protein expression.

**5. Mechanical Tension and Muscle Fiber Type:**
- While mechanical tension is a stimulus for hypertrophy, prolonged or excessive tension can trigger negative regulatory mechanisms to prevent excessive growth and maintain muscle function.
- Different muscle fiber types have different sensitivities to hypertrophy stimuli. Type I fibers are more resistant to hypertrophy than Type II fibers, potentially due to distinct regulatory mechanisms.

**6. Cellular Senescence:**
- Cellular senescence, the irreversible arrest of cell division, can contribute to muscle aging and reduced hypertrophy potential.

The intricate interplay of these pathways ensures that muscle growth is precisely regulated, preventing uncontrolled expansion and promoting muscle health. Understanding these negative regulatory mechanisms is crucial for developing strategies to enhance muscle growth in conditions like sarcopenia or muscle wasting diseases.'
"

Proteins (1)

Compounds (3)