Inverse Association Between Hypothalamic N-Acetyl Aspartate/Creatine Ratio and Indices of Body Mass in Adolescents with Obesity

• Published in: The Journal of nutrition 2022-03, Vol.152 (3), p.663-670
• Main Authors: Neves, Thaysa Mara Gazzotto, Simoes, Estefania, Otaduy, Maria Concepcíon García, Calfat, Elie Leal de Barros, Bertolazzi, Pâmela, da Costa, Naomi Antunes, Duran, Fábio Luís de Souza, Correia-Lima, Joanna, Martin, Maria da Graça Morais, Seelander, Marília Cerqueira Leite, Otani, Victor Henrique Oyamada, Otani, Thais Zélia dos Santos, Vasques, Daniel Augusto Corrêa, Filho, Geraldo Busatto, Kochi, Cristiane, Uchida, Ricardo Riyoiti
• Format: Article
• Language: English
• Subjects: Addictions; Adolescent; adolescent obesity; Adolescents; Amylin; Aspartic Acid - analogs & derivatives; Body mass; Body mass index; Body weight; brain damage; Case-Control Studies; Child; Choline; Choline - metabolism; Creatine; Creatine - metabolism; Crosstalk; Cytokines; Eating disorders; Eutrophication; Food habits; Food preferences; Ghrelin; Glutamic Acid - metabolism; Glutamine; Hormones; Humans; Hypothalamus; Insulin; Interleukin 8; Magnetic resonance spectroscopy; Metabolism; Metabolites; N-Acetylaspartate; neuroimaging; Neuropeptide Y; Obesity; Obesity and Eating Disorders; Pediatric Obesity; Phosphocholine; Serum proteins; spectroscopy; Teenagers; Weight control
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxab415

Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = −0.25; P = 0.03) and serum insulin (rho = −0.27; P = 0.04), C-peptide (rho = −0.26; P = 0.04), amylin (r = −0.27; P = 0.04), ghrelin (rho = −0.30; P = 0.02), and neuropeptide Y (r = −0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.