###### Abstract  
Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, health status, and genetic predisposition). The biological mechanisms by which PFAS might affect systems are largely unknown. To support the risk assessment process, AOP-helpFinder, a new artificial intelligence tool, was used to rapidly and systematically explore all available published information in the PubMed database. The aim was to identify existing associations between PFAS and metabolic health outcomes that may be relevant to support building adverse outcome pathways (AOPs). The collected information was manually organized to investigate linkages between PFAS exposures and metabolic health outcomes, including dyslipidemia, hypertension, insulin resistance, and obesity. Links between PFAS exposure and events from the existing metabolic-related AOPs were also retrieved. In conclusion, by analyzing dispersed information from the literature, we could identify some associations between PFAS exposure and components of existing AOPs. Additionally, we identified some linkages between PFAS exposure and metabolic outcomes for which only sparse information is available or which are not yet present in the AOP-wiki database that could be addressed in future research. AOP-helpFinder; adverse outcome pathways; metabolic syndrome; per- and polyfluoroalkyl substances; AOP-wiki Article  
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validated by the OECD), are accessible on the AOP-wiki database ([[https://aopwiki.org/](https://aopwiki.org/)]([https://aopwiki.org/](https://aopwiki.org/)), accessed on 28 February 2022) [5]. Per- and polyfluoroalkyl substances (PFAS) are a very large group of xenobiotics that are used for a multitude of applications due to their unique physicochemical properties (e.g., heat and acid resistance, water and oil repellency, and high surface activity) (see [PERSON] and co-workers [6]). PFAS are persistent and ubiquitous in the environment, and measurable levels of some PFAS are detected in human populations globally [7]. Toxicological and epidemiological studies have reported that exposure to certain PFAS and/or their mixtures may potentially interfere with a wide range of adverse health effects [8]; for instance, thyroid disruption, reproductive toxicity, reduced birth weight, various metabolic outcomes, and decreased immune responsiveness [9; 10]. While a number of studies reported that exposure to certain PFAS (e.g., PFOA, PPOS, PFHoS, and PFNA) may significantly result in dyslipidemia (i.e., elevated triglycerides and total cholesterol and increased low-density lipoproteins (LDL)), hypertension (i.e., elevated blood pressure), obesity (i.e., elevated waist circumference), and insulin resistance/hyperglycemia (i.e., elevated fasting glucose), some studies published conclusions with disparities [11; 12]. These metabolic outcomes, also known as components of metabolic syndrome [12], contribute to the risk of developing cardiovascular disease (CVD), which is the leading cause of death worldwide [13; 14; 15]. In general, the underlying biological mechanisms that explain how exposure to PFAS leads to these reported adverse health outcomes remain inconclusive. Similar to other persistent organic pollutants (POPs), PFAS interact with various nuclear receptors, including peroxisome-proliferator-activated receptors (PPARs), estrogen receptors (ERs), and the pregnane X receptor (PXR); however, the main reported mechanism is PPAR activation [16; 17]. Currently, only one AOP initiated by perfluorooctanoic acid (PFOA), described as stressor, is available and citable [18]. AOP-166 starts with the activation of PPAR alpha (PPAR\(\alpha\)) as an MIE linking it to the AO of pancreatic acinar tumors in rodents [18].