Melanocortin antagonism ameliorates muscle wasting and inflammation in chronic kidney disease
Open accessAbstract
Aberrant melanocortin signaling has been implicated in the pathogenesis of wasting in chronic kidney disease (CKD). Previously, we demonstrated that agouti-related peptide (AgRP), a melenocortin-4 receptor antagonist, reduced CKD-associated cachexia in CKD mice. Our previous studies with AgRP utilized dual energy X-ray (DXA) densitometry to assess the body composition in mice (Cheung W, Kuo HJ, Markison S, Chen C, Foster AC, Marks DL, Mak RH. J Am Soc Nephrol 18: 2517-2524, 2007; Cheung W, Yu PX, Little BM, Cone RD, Marks DL, Mak RH. J Clin Invest 115: 1659-1665, 2005). DXA is unable to differentiate water content in mice, and fluid retention in CKD may lead to an overestimate of lean mass. In this study, we employed quantitative magnetic resonance technique to evaluate body composition change following central administration of AgRP in a CKD mouse model. AgRP treatment improved energy expenditure, total body mass, fat mass, and lean body mass in CKD mouse. We also investigated the effect of CKD-associated cachexia on the signaling pathways leading to wasting in skeletal muscle, as well as whether these changes can be ameliorated by central administration of AgRP. AgRP treatment caused an overall decrease in proinflammatory cytokines, which may be one important mechanism of its effects. Muscle wasting in CKD may be due to the activation of proteolytic pathways as well as inhibition of myogenesis and muscle regeneration processes. Our results suggest that these aberrant pathological pathways leading to muscle wasting in CKD mice were ameliorated by central administration of AgRP.
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Melanocortins play an important role in regulating blood pressure and sympathetic nervous system activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.
“Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [7]
The melanocortin system also plays an important role in regulating sympathetic nervous system activity and blood pressure besides its effects on food intake and body weight regulation.
“Besides its effects on food intake and body weight regulation, the melanocortin system also plays an important role in regulating SNS activity and BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [7]
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- Authors
- Cheung, W. W., & Mak, R. H.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Mak, Robert H.
- ORCID
- Mak, Robert H.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2012-11-01
- Volume
- 303
- Issue
- 9
- Pages
- F1315-F1324
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC3518185
- OpenAlex
- W2027010873
- Cited by
- 47
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 8 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK-3012, DK059630, K24-DK-59524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- chronic kidney disease, muscle atrophy, cachexia, agouti-related protein, melanocortin-4 receptor, body composition, quantitative MRI, energy expenditure, inflammatory cytokines, skeletal muscle proteolysis, myogenesis, muscle regeneration, fluid retention
- MeSH terms
- Animals, Body Composition, Cachexia, Disease Models, Animal, Inflammation, Male, Mice, Inbred C57BL, Nephrectomy, Signal Transduction, Cytokines, Muscle Weakness, Receptor, Melanocortin, Type 4, Mice, Renal Insufficiency, Chronic, Melanocortins, Agouti-Related Protein
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