Which adipokines (adipose tissue-derived hormones) are associated with skeletal muscle dysfunction?

Adipokines Associated with Skeletal Muscle Dysfunction

Leptin and adiponectin are the primary adipokines associated with skeletal muscle dysfunction, with leptin contributing to muscle dysfunction through inflammatory pathways and adiponectin typically playing a protective role when present in adequate levels. 1

Key Adipokines and Their Effects on Muscle Function

Leptin

• Mechanisms of muscle dysfunction:
  • Promotes inflammatory pathways in muscle tissue
  • Contributes to intramuscular lipid accumulation
  • Associated with skeletal muscle insulin resistance, particularly in obesity 1
  • High circulating levels correlate with reduced muscle strength 2
  • Paradoxically, complete absence of leptin is also detrimental to muscle mass and strength 3

Adiponectin

• Role in muscle function:
  • Has anti-inflammatory and insulin-sensitizing properties 4, 1
  • Levels are inversely correlated with adiposity and insulin resistance 1
  • Higher adiponectin levels in older adults are associated with reduced quadriceps torque and handgrip strength 2
  • Enhances glucose uptake and increases fatty acid oxidation in skeletal muscle 5

Resistin

• Associated with insulin resistance 4
• Inversely associated with quadriceps torque in older adults 2
• The resistin/IGF-1 ratio is inversely associated with muscle strength 2

Pathophysiological Mechanisms

1. Adipose Tissue Dysfunction:

   • Adipose tissue becomes dysfunctional in obesity, leading to inflammation, fibrosis, disruptions in angiogenesis, and alterations in adipokine release 4
   • This dysfunction influences insulin sensitivity, energy balance, and other metabolic control points 4

2. Intramuscular Lipid Accumulation:

   • Skeletal muscle infiltration of adipose tissue correlates with insulin resistance 4
   • In lean individuals with poorly controlled T1D, higher intramuscular lipid content is a marker of insulin resistance 4

3. Inflammatory Pathways:

   • Adipokines communicate between adipose tissue and skeletal muscle 6
   • When feed intake exceeds energy expenditure, adipokines become dysregulated, causing lipotoxicity in skeletal muscle 5

4. AMPK Signaling:

   • Adiponectin and leptin enhance glucose uptake and increase fatty acid oxidation in skeletal muscle through activation of AMPK 5
   • This causes phosphorylation and inhibition of ACC, decreasing availability of malonyl CoA 5

Clinical Implications

1. Assessment of Muscle Function:

   • Evaluate intramuscular lipid content as a marker of insulin resistance 1
   • Monitor leptin and adiponectin levels in relation to muscle strength 2
   • The ratio of leptin to adiponectin may be directly associated with handgrip strength 2

2. Therapeutic Approaches:

   • Exercise interventions can increase adiponectin levels and improve muscle function 1
   • Weight loss through lifestyle modifications is the primary intervention for managing high leptin levels 1
   • Anti-inflammatory diet rich in omega-3 fatty acids, antioxidants, and phytonutrients may help regulate leptin levels 1

Common Pitfalls and Caveats

• Focusing only on weight loss medications without addressing lifestyle factors is ineffective 1
• Overlooking the importance of sustained lifestyle changes can lead to treatment failure 1
• Neglecting the multisystem effects of adipokines beyond muscle function may miss important clinical implications 1
• The relationship between adipokines and muscle function is complex - both excess and deficiency can be problematic 3

Monitoring Recommendations

• Follow leptin and adiponectin levels along with measures of muscle strength and function 1
• Monitor inflammatory markers and metabolic parameters to assess the effectiveness of interventions 1
• Evaluate both muscle mass and strength, as adipokines may affect them differently 2

Understanding the complex interplay between adipokines and skeletal muscle function provides insights into the pathophysiology of muscle dysfunction and potential therapeutic targets for improving muscle health and function.