Molecular Pathways Linking High-Fat Diet and PM_2.5 Exposure to Metabolically Abnormal Obesity: A Systematic Review...

Obesity, influenced by environmental pollutants, can lead to complex metabolic disruptions. This systematic review and meta-analysis examined the molecular mechanisms underlying metabolically abnormal obesity caused by exposure to a high-fat diet (HFD) and fine particulate matter (PM_2.5). Following the PRISMA guidelines, articles from 2019 to 2024 were gathered from Scopus, Web of Science, and PubMed, and a random-effects meta-analysis was performed, along with subgroup analyses and pathway enrichment analyses. This study was registered in the Open Science Framework. Thirty-three articles, mainly case-control studies and murine models, were reviewed, and they revealed that combined exposure to HFD and PM_2.5 resulted in the greatest weight gain (82.835 g, p = 0.048), alongside increases in high-density lipoproteins, insulin, and the superoxide dismutase. HFD enriched pathways linked to adipocytokine signaling in brown adipose tissue, while PM_2.5 impacted genes associated with fat formation. Both exposures downregulated protein metabolism pathways in white adipose tissue and activated stress-response pathways in cardiac tissue. Peroxisome proliferator-activated receptor and AMP-activated protein kinase signaling pathways in the liver were enriched, influencing non-alcoholic fatty liver disease. These findings highlight that combined exposure to HFD and PM_2.5 amplifies body weight gain, oxidative stress, and metabolic dysfunction, suggesting a synergistic interaction with significant implications for metabolic health.