Interventional approaches to combat obesity: Exploring the metabolomic signature of weight loss trials

Affiliations

¹ Immunonutrition Unit, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece.
² Laboratory of Pharmaceutical Technology, Division of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
³ Laboratory of Clinical Nutrition and Dietetics, Department of Nutrition and Dietetics, School of Physical Education, Sports Science and Dietetics, University of Thessaly, 42100, Trikala, Greece.
⁴ Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, University Hospital, Alexandroupolis, Greece.
⁵ Department of Nutritional Science and Dietetics, School of Health Sciences, University of the Peloponnese, GR-24100, Kalamata, Greece.
⁶ Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece.
⁷ Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece.
⁸ Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, 56429, Thessaloniki, Greece.

PMID: 40678167
PMCID: PMC12269453
DOI: 10.1016/j.metop.2025.100373

Review

Interventional approaches to combat obesity: Exploring the metabolomic signature of weight loss trials

Eleni C Pardali et al. Metabol Open. 2025.

. 2025 Jun 24:27:100373.

doi: 10.1016/j.metop.2025.100373. eCollection 2025 Sep.

Authors

Affiliations

¹ Immunonutrition Unit, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece.
² Laboratory of Pharmaceutical Technology, Division of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
³ Laboratory of Clinical Nutrition and Dietetics, Department of Nutrition and Dietetics, School of Physical Education, Sports Science and Dietetics, University of Thessaly, 42100, Trikala, Greece.
⁴ Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, University Hospital, Alexandroupolis, Greece.
⁵ Department of Nutritional Science and Dietetics, School of Health Sciences, University of the Peloponnese, GR-24100, Kalamata, Greece.
⁶ Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece.
⁷ Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece.
⁸ Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, 56429, Thessaloniki, Greece.

PMID: 40678167
PMCID: PMC12269453
DOI: 10.1016/j.metop.2025.100373

Abstract

Obesity is characterized by the expansion of adipose tissue, contributing to systemic low-grade inflammation, insulin resistance, and widespread disruption of metabolic pathways. These pathophysiological changes are strongly linked to the development of several chronic conditions, including metabolic syndrome, type 2 diabetes, cardiovascular disease, and certain forms of cancer. Metabolomics have emerged as a powerful analytical approach for elucidating obesity-related metabolic disturbances at both the cellular and systemic levels, enabling the identification of specific metabolic signatures associated with disease risk and progression. This narrative review synthesizes findings from interventional weight loss studies that addressed obesity using various strategies, including dietary modification, physical activity, pharmacotherapy, and bariatric surgery. Focusing on studies employing metabolomic techniques, this review highlights both consistent and divergent patterns in metabolite changes observed following weight loss, particularly in the metabolism of amino acids, lipids, short-chain fatty acids, and other metabolic pathways affected by each intervention. These insights have the potential to inform the development of more personalized and effective therapeutic approaches for obesity, thereby advancing the implementation of precision medicine in obesity management.

Keywords: Amino acids; Bariatric surgery; Lipids; Metabolism; Physical exercise; Short-chain fatty acids; Weight loss.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Given her role as co Editor in chief, Maria Dalamaga had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
The impact of dietary and lifestyle interventions on amino acids, their derivatives, and broader metabolic profiles. 1,5-AG: 1,5-anhydroglucitol; 2-HB: 2-hydroxybutyrate; AcAc: acetoacetate; Ala: alanine; Arg: arginine; Asn: asparagine; Asp: aspartic acid; BHB: 3-β-hydroxybutyrate; BT: behavioral therapy; Cit: citrulline; CT: controlled trial; Cys: cysteine; DIRECT: Dietary Intervention Randomized Controlled Trial; Gln: glutamine; Glu: glutamic acid; Gly: glycine; HD: hypocaloric diet; HGI: high-glycemic index; His: histidine; HLCD: healthy low carbohydrate diet; HMD: hypocaloric Mediterranean diet; Ile: isoleucine; Leu: leucine; LFD: low-fat diet; LGI: low-glycemic index; LI: lifestyle intervention; Lys: lysine; Met: methionine; Orn: ornithine; PA: physical activity; Phe: phenylalanine; POUNDS LOST: Preventing Overweight Using Novel Dietary Strategies Trial; Pro: proline; RCT: randomized controlled trial; SCFAs: short-chain fatty acids; Ser: serine; Tau: taurine; TCA: tricarboxylic acid cycle; Thr: threonine; TMA: trimethylamine; TMAO: trimethylamine N-oxide; Trp: tryptophan; Tyr: tyrosine; Val: valine; VLCD: very low carbohydrate diet; VLCKD: very-low-calorie ketogenic diet; β-Ala: β-alanine. ↑: increased after the intervention; ↓: decreased after the intervention, ↔: remained unchainged after the intervention.

**Fig. 2**
Alterations in lipid and lipid-derived metabolite levels following dietary and lifestyle interventions. AC: acylcarnitine; ae: ester bonds; CAR: carnitine; Cer: ceramide; ee: ether bonds; HD: hypocaloric diet; HD + PA: hypocaloric diet plus physical activity; HGI: high-glycemic index; LCD: low-carbohydrate diet; LFD: low-fat diet; LGI: low-glycemic index; LI: lifestyle intervention; LysoPC: lysophosphatidylcholine; PC: phosphatidylcholine; SM: sphingomyelins; VLCD: very low-carbohydrate diet; WL: weight loss. ↑: increased after the intervention; ↓: decreased after the intervention, ↔: remained unchainged after the intervention.

**Fig. 3**
Exercise-induced alterations in metabolite levels. Ala: alanine; Asn: asparagine; Asp: aspartic acid; Β-HIB: 3-hydroxyisobutyric acid; GABA: γ-aminobutyric acid; Gln: glutamine; Glu: glutamic acid; Gly: glycine; His: histidine; Ile: isoleucine; KIC: alpha-ketoisocaproate; Leu: leucine; Lys: lysine; Orn: ornithine; Phe: phenylalanine; Pro: proline; Pyr: pyruvate; SCFAs: short-chain fatty acids; Ser: serine; TCA: tricarboxylic acid cycle; Thr: threonine; Tyr: tyrosine; Val: valine. ↑: increased after the intervention; ↓: decreased after the intervention, ↔: remained unchainged after the intervention.

**Fig. 4**
Postoperative alterations in metabolite profiles after bariatric surgery. 1,5-AG: 1,5-anhydroglucitol; 2-HB: 2-hydroxybutyrate; AcAc; acetoacetate; Ala: alanine; BHB: 3-β-hydroxybutyrate; CAR: carnitine; Cer: ceramide; Glu: glutamic acid; GlucA: glucuronic acid; Gly: glycine; Ile: isoleucine; KIC: α-ketoisocaproate; Leu: leucine; Lys: lysine; Met: methionine; PCaa: phosphatidylcholine diacyl; PCs: phosphatidylcholines; Phe: phenylalanine; Pyr: pyruvate; Ser: serine; TCA: tricarboxylic acid cycle; Tau: taurine; TMAO: trimethylamine n-oxide; Trp: tryptophan; Tyr: tyrosine; Val: valine; β-Ala: β-alanine. ↑: increased after the intervention; ↓: decreased after the intervention, ↔: remained unchainged after the intervention.

**Fig. 5**
Alterations in metabolite levels after pharmacological therapy for weight loss. 2-HB: 2-hydroxybutyrate; AcAc: acetoacetate; Ala: alanine; Asn: asparagine; BHB: 3-β-hydroxybutyrate; CAR: carnitine; Cys: cysteine; DHA: docosanoic acid; Glu: glutamic acid; Gly: glycine; Ile: isoleucine; KIC: α-ketoisocaproate; Leu: leucine; Met: methionine; Phe: phenylalanine; PUFA: polyunsaturated fatty acids; SCFAs: short chain fatty acids; Ser: serine; TCA: tricarboxylic acid cycle; Thr: threonine; TMAO: trimethylamine n-oxide; Trp: tryptophan; Tyr: tyrosine; Val: valine; α-ΚIV: α-ketoisovalerate. ↑: increased after the intervention; ↓: decreased after the intervention, ↔: remained unchainged after the intervention.

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Interventional approaches to combat obesity: Exploring the metabolomic signature of weight loss trials

Affiliations

Interventional approaches to combat obesity: Exploring the metabolomic signature of weight loss trials

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources