Brief Report - (2025) Volume 26, Issue 5
Received: 06-Nov-2025, Manuscript No. IPP-25-23008; Editor assigned: 08-Nov-2025, Pre QC No. IPP-25-23008; Reviewed: 22-Nov-2025, QC No. IPP-25-23008; Revised: 28-Nov-2025, Manuscript No. IPP-25-23008; Published: 06-Dec-2025
Metabolic Syndrome (MetS) has evolved from a purely metabolic entity to a complex immunometabolic disorder in which chronic low grade inflammation, adipokine imbalance and oxidative stress play major roles. Recent evidence, including our cross-sectional study of 504 Turkish adults, showed that 32.7% met MetS criteria and 15.5% exhibited positive autoimmune markers (ENA/FANA) without overt autoimmune disease. This review highlights the pancreas as a central organ influenced by both metabolic overload and immune activation, emphasizing early detection opportunities to prevent β-cell dysfunction and autoimmune pancreatitis.
Metabolic syndrome, Autoimmunity, Pancreas, Inflammation, ENA, FANA, Adipokines, Endocrine-immune axis
Metabolic Syndrome (MetS) represents a cluster of abnormalities including central obesity, dyslipidemia, insulin resistance, and hypertension. Although typically classified as a metabolic condition, MetS has clear inflammatory and autoimmune components [2,3]. Adipose tissue acts as an endocrine organ releasing cytokines such as TNF-α, IL-6, and resistin, which disrupt insulin signaling and increase oxidative stress [4,5]. These cytokines can also stimulate antigen-presenting cells, facilitating loss of immune tolerance [6].
In Mediterranean populations, including Turkiye, a combination of high dietary fat, obesity and vitamin D deficiency enhances inflammatory tone and promotes autoimmune reactivity [7]. Such metabolic-immune overlap may explain the rising coexistence of MetS and subclinical autoimmune markers in epidemiologic studies [1,8].
Endocrine-Immune Cross-Talk in Metabolic Syndrome
Visceral adiposity drives macrophage infiltration and T-cell activation within adipose tissue, maintaining a lowgrade chronic inflammation known as “metaflammation” [2,9]. Leptin promotes Th1 polarization and inhibits T-regulatory function, thus bridging obesity and autoimmunity [10]. Cytokines such as IL-1β and TNF-α activate the NF-κB and JNK pathways, impairing insulin signaling and β-cell function [11].
Autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis exhibit increased prevalence of insulin resistance, further supporting a bidirectional relationship between metabolism and immunity [12,13]. Thus, immune dysregulation is both a cause and consequence of metabolic stress.
Pancreatic Involvement and Mechanistic Insights
The pancreas is especially sensitive to inflammatory mediators derived from adipose tissue. Lipotoxicity and chronic hyperglycemia lead to endoplasmic reticulum stress in β-cells, triggering MHC expression and presentation of self-antigens [14]. These events make β-cells immunogenic, susceptible to T-cell-mediated destruction. Circulating islet autoantibodies have been identified in up to 10-20% of MetS patients without overt diabetes, suggesting early immune sensitization [8,15].
Exocrine pancreatic involvement has also been observed in metabolic inflammation, with infiltration of CD4+ and CD8+ lymphocytes and increased oxidative stress markers [16]. Distinguishing between metabolic and autoimmune pancreatitis requires attention to cytokine profiles and imaging findings.
Evidence from the Turkish Cohort
In our Turkish cohort study, 504 adults were screened for metabolic and autoimmune parameters [1]. We found that 32.7% had MetS and 15.5% were ENA/FANA positive in the absence of clinical autoimmune disease. The coexistence of obesity, hypertriglyceridemia and autoimmune seropositivity supports a link between chronic inflammation and early immune activation. Similar findings have been observed in Korean and Japanese populations, confirming that subclinical autoimmunity may emerge during prolonged metabolic stress [8,17].
Importantly, the positive antibody group demonstrated higher CRP and ALT levels, implying that hepatic and pancreatic inflammation could be early indicators of immune-metabolic interplay.
Future Directions
Further research should aim to identify immunometabolic biomarkers that predict β-cell decline or autoimmune transition. Multi-omics approaches combining cytokine, adipokine and transcriptomic profiling could unravel shared signaling nodes [18]. Investigating the efficacy of anti-inflammatory interventions (e.g., GLP-1 analogues, SGLT2 inhibitors, omega-3 fatty acids) on immune modulation may also reveal new treatment paradigms [19]. Finally, prospective studies using pancreatic imaging and functional testing can clarify how metabolic inflammation evolves into true autoimmune pathology.
Metabolic syndrome and autoimmune disorders share overlapping inflammatory pathways centered around adipose-pancreas communication. The recognition of subclinical autoimmunity within MetS patients could redefine early preventive endocrinology. The pancreas, as a dual endocrine-immune target, exemplifies how chronic metabolic load may transform into immune activation and tissue damage.
Early identification of these interactions may allow timely interventions before irreversible β-cell loss or autoimmune pancreatitis develops.
The author declares no conflicts of interest.
No external funding was received.
Fatih Oner Kaya: Concept, data interpretation, literature review, manuscript writing.
This paper provided a comparative analysis of social democracy and Fascism. Social democracy adheres to protecting the autonomy of an individual, while Fascism rejects individualism and egalitarianism.
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Citation: Kaya FO (2025) Pancreatic Involvement in Metabolic-Autoimmune Cross-Talk: Emerging Evidence from Turkiye. J Pancreas. 26:943
Copyright: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
