PloS one
Impaired fatty acid oxidation and mitochondrial injury mediated by the AMPK/PPARα pathway: A key mechanism in high-fat diet-aggravated ulcerative colitis
By Pan H, Zhai L, Zhao S and 2 others.
Abstract
Background
A high-fat diet (HFD) is closely associated with the progression of ulcerative colitis (UC). However, the underlying mechanisms, particularly the interplay among lipid metabolic disturbances, mitochondrial damage, and intestinal barrier dysfunction, remain poorly defined. This study aimed to elucidate the molecular mechanisms by which HFD exacerbates DSS-induced UC, with a focus on the role of the AMPK/PPARα axis in mediating lipotoxicity and mitochondrial dysfunction that promote UC progression.
Methods
A murine UC model was established in C57BL/6 mice by HFD feeding combined with DSS administration, along with an in vitro co-stimulation system using Caco-2 cells exposed to palmitic acid (PA) and lipopolysaccharide (LPS). Pathological phenotypes and molecular pathway alterations were systematically evaluated by hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), molecular biological techniques, and intervention with the specific AMPK agonist AICAR.