2-Aminoadipic acid (2-AAA) as a potential biomarker for insulin resistance in childhood obesity

• Published in: Scientific reports Vol. 9; no. 1; pp. 13610 - 10
• Main Authors: Lee, Hyo Jung, Jang, Han Byul, Kim, Won-Ho, Park, Keon Jae, Kim, Kwang Youl, Park, Sang Ick, Lee, Hye- Ja
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.09.2019; Nature Publishing Group
• Subjects: 2-Aminoadipic Acid - analysis; 2-Aminoadipic Acid - blood; 2-Aminoadipic Acid - metabolism; 631/80/86; 692/53/2423; 82; 82/80; Adipocytes; Adipocytes - metabolism; Adipogenesis; Adipogenesis - physiology; Adipose Tissue - metabolism; Adiposity; Adolescent; Animal models; Animals; Biomarkers; Biomarkers - blood; Blood Glucose - metabolism; Body fat; Body Mass Index; Cell culture; Cell Differentiation - physiology; Child; Children; Cohort Studies; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Energy storage; Female; Follow-Up Studies; Gluconeogenesis; Glucose; Hepatocytes; Humanities and Social Sciences; Humans; Insulin; Insulin - metabolism; Insulin resistance; Insulin Resistance - physiology; Leptin - metabolism; Male; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; multidisciplinary; Obesity; Pediatric Obesity - metabolism; Pediatric Obesity - physiopathology; Republic of Korea; Science; Science (multidisciplinary); Skeletal muscle; Triglycerides; Triglycerides - metabolism; Waist Circumference; Republic of Korea
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49578-z

Insulin resistance is an important clinical feature of metabolic syndrome, which includes obesity and type 2 diabetes. Increased adipose energy storage in obesity promote insulin resistance and other metabolic adverse effects. To identify a new link between adipocyte and insulin resistance, we performed targeted metabolite profiling of differentiated adipocytes and studied the association between adipogenic metabolites and insulin resistance. We found a correlation between 2-aminoadipic acid (2-AAA) and adipogenic differentiation. Also, circulatory 2-AAA was positively associated with obesity-related factors (fat mass, fat percent, waist circumference, BMI, BMI z -score, triglycerides, insulin, and HOMA-IR) at baseline and after 2 years in the children cohort study. Of these factors, increased BMI z -score and HOMA-IR were the primary independent factors associated with higher 2-AAA levels, and the baseline 2-AAA level was an indicator of the BMI z -score after 2 years. To validate the relationship between 2-AAA and obesity-related factors, we analyzed changes in 2-AAA levels following obesity intervention programs in two independent studies. In both studies, changes in 2-AAA levels during the intervention period were positively correlated with changes in the BMI z -score and HOMA-IR after adjusting for confounders. Moreover, the 2-AAA levels were increased in cell and mouse models of obesity-related insulin resistance. Excess 2-AAA levels led to impaired insulin signaling in insulin-sensitive cells (liver, skeletal muscle and adipose cells) and caused abnormal gluconeogenesis. Our results demonstrate that 2-AAA is associated with adipogenesis and insulin resistance. In this regard, 2-AAA could be a potential biomarker of obesity and obesity-related metabolic disorders.