Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans

• Published in: Molecular nutrition & food research Vol. 65; no. 20; pp. e2100164 - n/a
• Main Authors: Mayneris‐Perxachs, Jordi, Meikle, Peter, Mousa, Aya, Naderpoor, Negar, Fernández‐Real, José Manuel, Courten, Barbora
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2021
• Subjects: adipokines; Adipose tissue; adiposity; Adult; Arachidonic acid; blood serum; Body weight; brain; Cardiac muscle; Cardiovascular diseases; Carnosine; Carnosine - analysis; Carnosine - physiology; Cytokines; Dipeptidases - blood; Dipeptidases - physiology; Female; food research; Gangliosides; Glucose; Glucose - metabolism; Health risks; Homeostasis; Humans; Inflammation; Insulin; Insulin Resistance; interleukin-18; Interleukin-18 - blood; iron; Learning algorithms; lipidomics; Lipids; Lipids - blood; Machine learning; Male; metabolism; muscle; Muscle, Skeletal - chemistry; Muscles; myocardium; nutrition; obesity; Obesity - metabolism; Overweight; Overweight - metabolism; Phosphatidylethanolamine; phosphatidylethanolamines; Plasmalogens - physiology; Risk analysis; Risk factors; secretion; Skeletal muscle; Supplements; Young Adult; iron; carnosine; lipidomics; obesity; muscle
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.202100164

Introduction Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase‐1 with cardiometabolic risk factors and the lipidome. Methods and Results This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold‐standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2‐h glucose concentrations, whereas serum carnosinase‐1 levels are negatively associated with insulin sensitivity and positively with IL‐18. O‐PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid‐containing plasmalogens. Carnosinase‐1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase‐1. Conclusion These associations reinforce the role of muscle carnosine and serum carnosinase‐1 in the interplay among low‐grade chronic inflammation, glucose homeostasis, and insulin sensitivity. Carnosine has shown to improve glucose metabolism and cardiovascular risk. This study explores the relationship with the plasma lipidome by profiling >450 lipid species. Muscle carnosine and serum carnosinase‐1 activity (CN1) were negatively associated with 2‐h glucose and insulin sensitivity, respectively. This study identifies a strong association of carnosine and CN1 with plasmalogens containing arachidonic acid, a precursor of inflammatory mediators. The results of this study highlight the close link among carnosine, low‐grade chronic inflammation, and glucose homeostasis.