RESUMEN
Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.
Asunto(s)
Deficiencia de Colina , Hígado Graso , Enfermedades Gastrointestinales , Enfermedades Intestinales , Femenino , Humanos , Ratones , Animales , Niño , Deficiencia de Colina/complicaciones , Lactancia , Hígado Graso/metabolismo , Colina , Fosfatidilcolinas/metabolismo , Adenosina Trifosfatasas/metabolismo , Proteínas de Transferencia de Fosfolípidos/metabolismoRESUMEN
Group A streptococcus-associated severe invasive infection (streptococcal toxic shock syndrome) has been described. Streptococcal toxic shock syndrome occurs when the infecting strain of group A streptococcus produces superantigens. Confusion and combativeness are well known as the common symptoms of streptococcal toxic shock syndrome. We encountered a child who suffered from pyogenic sacroiliitis, with confusion and combativeness. Group A streptococcus was isolated from the patient's blood culture. However, his disease did not fulfill the criteria of streptococcal toxic shock syndrome. Pyogenic sacroiliitis in children is rare, but patients with pyogenic sacroiliitis due to group A streptococcus infection could show confusion and combativeness as clinical signs, similar to the signs in streptococcal toxic shock syndrome.