MULTIFACTORIAL DETERMINANTS OF OBESITY: THE ROLES OF HORMONES, GENETICS, INFLAMMATION AND GUT MICROBIOTA – REVIEW

Wiktor Śliwiński; Karolina Zarówna; Weronika Pura; Dominika Matecka; Mateusz Kosowski; Daniel Chołuj; Jakub Marciniak; Jakub Mazur

doi:10.31435/ijitss.4(48).2025.4311

Authors

Wiktor Śliwiński Independent Public Healthcare Institution of the Ministry of the Interior and Administration in Łódź, Łódź, Poland https://orcid.org/0009-0003-3584-9776
Karolina Zarówna District Hospital Complex in Oleśnica, Oleśnica, Poland https://orcid.org/0009-0003-6066-7667
Weronika Pura Independent Public Healthcare Institution of the Ministry of the Interior and Administration in Łódź, Łódź, Poland https://orcid.org/0009-0007-2889-667X
Dominika Matecka Józef Struś Municipal Hospital, Multispecialty Medical Centre in Poznań, Poznań, Poland https://orcid.org/0009-0000-4644-5943
Mateusz Kosowski Independent Public Healthcare Institution in Koło, Koło, Poland https://orcid.org/0009-0001-0811-5326
Daniel Chołuj Independent Public Healthcare Institution of the Ministry of the Interior and Administration in Łódź, Łódź, Poland https://orcid.org/0009-0009-1445-6336
Jakub Marciniak University Clinical Hospital No. 2 of the Medical University of Łódź, Łódź, Poland https://orcid.org/0009-0004-5675-6963
Jakub Mazur Voivodeship Combined Hospital in Kielce, Kielce, Poland https://orcid.org/0009-0005-1089-9210

DOI:

https://doi.org/10.31435/ijitss.4(48).2025.4311

Keywords:

Obesity, Hormones, Gut Microbiota, Inflammation, Treatment

Abstract

Obesity is a multifactorial chronic disease resulting from the interaction of genetic, hormonal, inflammatory, and microbial factors. While caloric imbalance contributes to its pathogenesis, pathways involving molecular mechanisms—such as leptin–melanocortin pathway dysfunction, adipokine dysregulation, and microbiota-induced inflammation—are also significant. Adipose tissue inflammation is characterized by macrophage infiltration, activation of MAPK and NF-κB pathways, and abnormal adipokine secretion, all of which lead to insulin resistance and metabolic dysfunction. Genetic factors, including mutations in the LEP, LEPR, POMC, and MC4R genes, can disrupt appetite regulation and predispose individuals to early-onset obesity. Syndromic forms of obesity, such as Prader–Willi and Bardet–Biedl syndromes, further highlight chromosomal influences. Hormonal imbalances, including those involving ghrelin, GLP-1, and CCK, also affect energy expenditure and appetite regulation. Additionally, gut dysbiosis contributes to systemic inflammation through increased levels of lipopolysaccharides (LPS) and decreased production of short-chain fatty acids, which maintain metabolic endotoxemia. These patterns of evidence underscore the need for integrative interventions targeting endocrine, inflammatory, and microbial pathways. Further research is required to clarify gene– microbiota–hormone interactions and to develop personalized therapeutic intervention.

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