Suppression of fatty acid β-oxidation and energy deficiency as a cause of inhibitory effect of E. coli lipopolysaccharide on osmotic water transport in the frog urinary bladder

Abstract

Previously we showed that arginine-vasotocin (AVT)-stimulated osmotic water permeability (OWP) of the frog urinary bladder was decreased if the mucosal side of the bladder has been naturally colonized by Gram-negative bacteria, or if bacterial lipopolysaccharide (LPS) was introduced into the lumen of the isolated bladder (J. Exp. Zool., 2013, 319, 487–494). Taking into account that in different tissues and cell types, challenge with LPS causes significant metabolic shift and energy deficiency, we hypothesized that an LPS-induced decrease of AVT-stimulated OWP could depend on the reduction of fatty acid oxidation (FAO), which is important for generation of ATP in epithelia. Using an isolated frog Rana temporaria urinary bladder we showed that the AVT-induced increase of OWP did not depend on the external glucose, but was inhibited by oligomycin, an ATP-synthase inhibitor, and by etomoxir, an inhibitor of carnitine palmitoyltransferase-1. In primary cultured epithelial cells isolated from the bladder mucosa, LPS E. coli (25 μg/ml, 21 h), as well as etomoxir (100 μM), decreased FAO accompanied by triacylglycerol accumulation. Both drugs impaired mitochondrial functions demonstrated by decreased ATP production and a reduced maximal oxygen consumption rate (OCR) and OCR directed at ATP synthesis. Additionally, we found that LPS decreased the expression of peroxisome proliferator-activated receptor alpha, a key player in the regulation of FAO. These data indicate that the impairment of AVT-induced water transport in osmoregulatory epithelium caused by LPS depends at least partly on defects in FAO and FAO-dependent energy production.