{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:11:38Z","timestamp":1788959498718,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Gda\u0144sk Medical University","doi-asserted-by":"publisher","award":["01-30025\/0008359\/01\/MPK\/MPK\/0\/2025"],"award-info":[{"award-number":["01-30025\/0008359\/01\/MPK\/MPK\/0\/2025"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"award":["01-30025\/0008359\/01\/MPK\/MPK\/0\/2025"],"award-info":[{"award-number":["01-30025\/0008359\/01\/MPK\/MPK\/0\/2025"]}],"id":[{"id":"https:\/\/ror.org\/019sbgd69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background\/Objectives: Circulating amino acids are not only markers of nutritional status; in experimental and interventional models they have been linked to hepatic lipogenesis, lipoprotein assembly, mitochondrial fatty acid oxidation, and bile acid conjugation, which makes them plausible candidate correlates of obesity-related lipid dysregulation. Despite this, most metabolomic studies of excess adiposity have focused either on a single lipid parameter\u2014typically triglycerides\u2014or only on branched-chain amino acids (BCAAs). This pilot study was designed to generate hypotheses about these associations across the full standard lipid panel using a targeted 19-amino acid liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) panel in adults spanning the body mass index (BMI) spectrum, with an analytical framework oriented around lipid phenotype variance rather than body weight classification. The design is cross-sectional and the analysis exploratory; no causal or predictive claim is made. Methods: Targeted LC-MS\/MS quantification of 19 plasma amino acids was performed in 50 adults grouped as normal weight (n = 20; BMI 22 \u00b1 1.5 kg\/m2), overweight (n = 20; BMI 28 \u00b1 1.5 kg\/m2), or obese (n = 10; BMI 34 \u00b1 2.0 kg\/m2). The analytical framework included: (i) one-way analysis of variance (ANOVA) with Bonferroni correction; (ii) Pearson correlation analysis; (iii) principal component analysis (PCA) performed on the lipid profile itself with amino acid projection vectors; (iv) K-means clustering based on lipid phenotype (K = 3); (v) Ward-linkage hierarchical clustering of the amino acid\u2013lipid correlation matrix; (vi) Random Forest permutation importance for all four lipid outcomes; and (vii) composite lipid risk indices including atherogenic index (TG\/HDL-C) and non-HDL cholesterol. Results: A distinct amino acid correlation pattern was observed for each of the four lipid fractions. Triglycerides (TG) correlated most strongly with glutamic acid (r = 0.58) and inversely with glutamine (r = \u22120.58). High-density lipoprotein cholesterol (HDL-C) correlated most strongly with glutamic acid (r = \u22120.61) and serine (r = 0.49). The strongest correlates of low-density lipoprotein cholesterol (LDL-C) were phenylalanine (r = 0.56) and leucine (r = 0.56), and those of total cholesterol (TC) were leucine (r = 0.63) and, inversely, glycine (r = \u22120.54). The atherogenic index (TG\/HDL-C) increased 2.9-fold from normal to obese and was most strongly correlated with glutamic acid, isoleucine, and glycine. In the multivariable models the amino acid panel accounted for a modest share of the variance in TG (adjusted R2 = 0.43; F(19,30) = 2.97, p = 0.004) and HDL-C (adjusted R2 = 0.35; F(19,30) = 2.40, p = 0.016). For LDL-C and TC the adjusted R2 values were close to zero (0.06 for both) and the overall models were not statistically significant (both p &gt; 0.33); no interpretable amino acid signal was therefore present for these two fractions, and no predictors are reported for them. Lipid-based K-means clustering identified three lipid-phenotype clusters (Favorable, Intermediate, Adverse lipid profiles) with differences in amino acid z-scores. Conclusions: In this exploratory pilot cohort, lipid dysregulation in abnormal BMI was associated with two partially separable amino acid axes: a glutamic acid\u2013glutamine axis (TG and partially HDL-C), and a glycine\u2013serine putatively protective pattern opposing all atherogenic lipid parameters. These findings extend the established BCAA\u2013insulin-resistance paradigm and suggest that targeted amino acid profiling\u2014particularly for glutamic acid, leucine, glycine, and serine\u2014may serve as a way of discovering candidate biomarkers for further study for dyslipidemia in individuals with abnormal BMI.<\/jats:p>","DOI":"10.3390\/biom16091305","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:26:11Z","timestamp":1788956771000},"page":"1305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Amino Acid Profiles in Adults with Abnormal Body Mass Index: Associations with Triglycerides, HDL Cholesterol, LDL Cholesterol, and Total Cholesterol in an Exploratory Cross-Sectional Metabolomic Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-7617","authenticated-orcid":false,"given":"Marta","family":"Jaskulak","sequence":"first","affiliation":[{"name":"Department of Immunobiology and Environment Microbiology, Faculty of Health Sciences, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Iwona","family":"Rybakowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Physiology, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-4859","authenticated-orcid":false,"given":"Magdalena","family":"Gregorczyk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Physiology, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Klaudia","family":"Antoniak-Pietrynczak","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and Environment Microbiology, Faculty of Health Sciences, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Patrycja","family":"Jab\u0142o\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-3791","authenticated-orcid":false,"given":"Katarzyna","family":"Zorena","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and Environment Microbiology, Faculty of Health Sciences, Medical University of Gda\u0144sk, D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). 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