Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapieOct 3, 2025

Using ALIAmides to tackle metabolic syndrome through multiple actions

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 2, 2026

Abstract

Metabolic syndrome (MetS) significantly increases the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality.

MetS is characterized by central obesity, dyslipidemia, hypertension, and insulin resistance.
Hepatic involvement, such as metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH), is frequently associated with MetS.
Intestinal barrier dysfunction, referred to as 'leaky-gut syndrome,' and gut microbiota dysbiosis are linked to chronic low-grade inflammation in MetS.
Current therapies for MetS target individual risk factors but do not effectively address its multifactorial nature.
ALIAmides like palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) may provide a multi-targeted approach by activating specific receptors and restoring gut barrier integrity.

Simplified

Metabolic syndrome (MetS) represents a growing clinical challenge worldwide, significantly increasing cardiovascular disease and type 2 diabetes risk, and all-cause mortality. Defined by a constellation of risk factors, including central obesity, dyslipidemia, hypertension, and insulin resistance, MetS is frequently associated with hepatic involvement such as metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH). A growing body of evidence also highlights intestinal barrier dysfunction called "leaky-gut syndrome" and gut microbiota dysbiosis as key contributors to the chronic low-grade inflammation that underlies MetS. Current therapies, including statins, GLP-1 receptor agonists, SGLT2 inhibitors, and antihypertensives, target individual components of the syndrome but fail to address its multifactorial pathophysiology. Additionally, these therapies often demonstrate tolerability issues, limited long-term adherence and compliance, and potential side effects particularly in hepatic and metabolic contexts. ALIAmides such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are emerging as promising adjunctive agents for MetS. By activating PPARs, modulating immune responses, and restoring gut barrier integrity, these compounds provide a multi-targeted strategy that addresses the complex pathophysiology of MetS. This review summarizes current evidence on ALIAmides, highlighting their potential to complement standard care and improve long-term metabolic outcomes.

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Declaration of Competing Interest The authors declare no conflict of interest.

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Using ALIAmides to tackle metabolic syndrome through multiple actions

Abstract

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