Amino Acid Metabolic Signatures of Dynapenic Obesity in Older Adults: A (Principal Component Analysis) Pca-Based Sex-Stratified Analysis in the Bushehr Elderly Health Program Publisher



Kheirandish M ; Cheraghloo N ; Tavasoli N ; Razi F ; Farsi F ; Bioky AA ; Aghaei Meybodi HRA ; Khalagi K ; Heshmat R ; Najjar N ; Shirkouhi MA ; Nabipour I ; Shafiee G ; Larijani B
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Background: Dynapenic obesity (DO), the co-occurrence of muscle strength loss and obesity in aging adults, exacerbates metabolic dysfunction and disability risks. While amino acid (AA) dysregulation is implicated in both conditions, their combined metabolic signature remains unexplored. We aimed to identify sex-specific amino acid metabolic patterns associated with DO in Iranian older people. Methods: In this cross-sectional study of 1,928 adults (aged 50 years or older) from the Bushehr Elderly Health Program, serum AA profiles were quantified using UPLC-MS/MS. Principal component analysis (PCA) derived four factors from 20 AAs.Dynapenia thresholds were handgrip strength < 26 kg (men) and < 18 kg (women). Abdominal obesity was defined as a waist circumference ≥ 102 cm (men) or ≥ 88 cm (women). Multinomial logistic regression was used to evaluate the associations between these factors and dynapenia/obesity phenotypes, stratified by sex and adjusted for confounders. Results: The study included 1928 people (57.2% women; mean age 61.6 ± 7.7 years) after excluding subjects with missing values. Four distinct amino acid factors reflecting major metabolic pathways: insulin resistance with branched-chain and aromatic amino acids (Factor 1), nitrogen and methyl group metabolism (Factor 2), anabolic capacity and protein turnover (Factor 3), and urea cycle function and detoxification (Factor 4). In women, Factor 1(Leucine, Valine, Tyrosine, Alanine, Methionine, Tryptophan, and Proline) was positively linked to nondynapenic obesity [RR = 1.55 (1.15–2.08)] and DO [RR = 1.35(0.99–1.84, P = 0.059)], while Factor 4 (Citrulline, Ornithine, and Threonine) showed a protective effect against obesity [RR = 0.75(0.58–0.98)] in full models. In men, Factor 1 was associated with a higher risk of nondynapenic obesity [RR = 1.27(1.08–1.50)], and Factor 2 (Aspartic acid, Glutamic acid, Phenylalanine, Serine, Glycine, and Arginine) increased risk of dynapenia/non-obesity (RR = 1.34) and nondynapenic obesity (RR = 1.24). Factor 3 (Glutamine, Lysine, Asparagine, and Histidine) showed protective effects against obesity in men, emphasizing its anabolic capacity; however, after full adjustment, its significance disappeared. Conclusions: This study found distinct amino acid signatures associated with dynapenia and obesity in older adults. Factor 1 highlighted the role of insulin resistance-related amino acids in obesity across both genders, while Factor 2 emphasized nitrogen metabolism and its association with muscle loss and adiposity primarily in men. Factor 3’s anabolic profile suggested a complex but modest link to obesity and muscle health, and factor 4 underscored the protective effects of efficient nitrogen detoxification against obesity in women. These results reveal sex-specific metabolic pathways involved in dynapenic obesity, offering potential targets for personalized treatments to improve muscle and metabolic health in aging populations. Further research is needed to confirm these findings and explore therapeutic applications. © 2025 Elsevier B.V., All rights reserved.