What role does MC4R play in Müdigkeit?

MC4R (melanocortin-4 receptor) is a key regulator of energy balance and appetite. Mutations in MC4R are the most common monogenic cause of early-onset obesity. A direct causal link to fatigue is not well established. The indirect connection involves energy homeostasis: impaired MC4R signaling can alter eating behavior and reduce physical activity, which may secondarily contribute to fatigue. Animal studies also suggest MC4R involvement in sleep-wake regulation. In humans, effects are small and heavily confounded by lifestyle. Direct-to-consumer DNA tests reporting MC4R variants do not diagnose fatigue. Evidence is primarily mechanistic and from GWAS, not from clinical trials. A single MC4R variant does not explain chronic exhaustion. Persistent fatigue should be evaluated for other causes (iron deficiency, thyroid disorders, sleep apnea).