neuropeptide-y and Muscular-Atrophy

Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation.

Topics: Agouti-Related Protein; Animals; Dexmedetomidine; Endotoxemia; Hypothalamus; Inflammation; Interleukin-1; Male; Methylhistidines; Muscle, Skeletal; Muscular Atrophy; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. α-Melanocyte-stimulating hormone (α-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic α-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with α-MSH (50 μg/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake (P < 0.01). In addition, α-MSH decreased hypothalamic expression of IL-1β, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, α-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. α-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral α-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.

Topics: Agouti-Related Protein; alpha-MSH; Animals; Anorexia; Arthritis, Experimental; Cachexia; Cyclooxygenase 2; Hypothalamus; Interleukin-1beta; Male; Muscular Atrophy; Neuropeptide Y; Rats; Rats, Wistar