Raghd Abu Helal1, Lucia Russo2, Hilda E Ghadieh1, Harrison T Muturi1, Suman Asalla1, Abraham D Lee3, Cara Gatto-Weis4, Sonia M Najjar5. 1. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. 2. Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA. 3. Department of Rehabilitation Sciences, College of Health Sciences, The University of Toledo, Toledo, OH, USA. 4. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Department of Pathology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA. 5. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. Electronic address: najjar@ohio.edu.
Abstract
OBJECTIVE: NAFLD is a complex disease marked by cellular abnormalities leading to NASH. NAFLD patients manifest low hepatic levels of CEACAM1, a promoter of insulin clearance. Consistently, Cc1-/- null mice displayed spontaneous hyperinsulinemia/insulin resistance and steatohepatitis. Liver-specific reconstitution of Ceacam1 reversed these metabolic anomalies in 8-month-old Cc1-/-xliver+ mice fed a regular chow diet. The current study examined whether it would also reverse progressive hepatic fibrosis in mice fed a high-fat (HF) diet. METHODS: 3-Month-old mice were fed a high-fat diet for 3-5 months, and metabolic and histopathological analysis were conducted to evaluate their NASH phenotype. RESULTS: Reconstituting CEACAM1 to Cc1-/- livers curbed diet-induced liver dysfunction and NASH, including macrovesicular steatosis, lobular inflammation, apoptosis, oxidative stress, and chicken-wire bridging fibrosis. Persistence of hepatic fibrosis in HF-fed Cc1-/- treated with nicotinic acid demonstrated a limited role for lipolysis and adipokine release in hepatic fibrosis caused by Ceacam1 deletion. CONCLUSIONS: Restored metabolic and histopathological phenotype of HF-fed Cc1-/-xliver+xliver+ assigned a critical role for hepatic CEACAM1 in preventing NAFLD/NASH including progressive hepatic fibrosis.
OBJECTIVE: NAFLD is a complex disease marked by cellular abnormalities leading to NASH. NAFLD patients manifest low hepatic levels of CEACAM1, a promoter of insulin clearance. Consistently, Cc1-/- null mice displayed spontaneous hyperinsulinemia/insulin resistance and steatohepatitis. Liver-specific reconstitution of Ceacam1 reversed these metabolic anomalies in 8-month-old Cc1-/-xliver+ mice fed a regular chow diet. The current study examined whether it would also reverse progressive hepatic fibrosis in mice fed a high-fat (HF) diet. METHODS: 3-Month-old mice were fed a high-fat diet for 3-5 months, and metabolic and histopathological analysis were conducted to evaluate their NASH phenotype. RESULTS: Reconstituting CEACAM1 to Cc1-/- livers curbed diet-induced liver dysfunction and NASH, including macrovesicular steatosis, lobular inflammation, apoptosis, oxidative stress, and chicken-wire bridging fibrosis. Persistence of hepatic fibrosis in HF-fed Cc1-/- treated with nicotinic acid demonstrated a limited role for lipolysis and adipokine release in hepatic fibrosis caused by Ceacam1 deletion. CONCLUSIONS: Restored metabolic and histopathological phenotype of HF-fed Cc1-/-xliver+xliver+ assigned a critical role for hepatic CEACAM1 in preventing NAFLD/NASH including progressive hepatic fibrosis.
Authors: Sonia M Najjar; Yan Yang; Mats A Fernström; Sang-Jun Lee; Anthony M Deangelis; George A Abou Rjaily; Qusai Y Al-Share; Tong Dai; Tiffany A Miller; Shobha Ratnam; Randall J Ruch; Stuart Smith; Sue-Hwa Lin; Nicole Beauchemin; Ana Maria Oyarce Journal: Cell Metab Date: 2005-07 Impact factor: 27.287
Authors: Sumona G Lester; Lucia Russo; Simona S Ghanem; Saja S Khuder; Anthony M DeAngelis; Emily L Esakov; Thomas A Bowman; Garrett Heinrich; Qusai Y Al-Share; Marcia F McInerney; William M Philbrick; Sonia M Najjar Journal: Front Endocrinol (Lausanne) Date: 2015-08-03 Impact factor: 5.555
Authors: Raghd Abu Helal; Harrison T Muturi; Abraham D Lee; Wei Li; Hilda E Ghadieh; Sonia M Najjar Journal: Int J Mol Sci Date: 2022-04-14 Impact factor: 6.208
Authors: Sonia M Najjar; Raziyeh Abdolahipour; Hilda E Ghadieh; Marziyeh Salehi Jahromi; John A Najjar; Basil A M Abuamreh; Sobia Zaidi; Sivarajan Kumarasamy; Harrison T Muturi Journal: Biomedicines Date: 2022-08-05
Authors: Zhifang Zhang; Deirdre La Placa; Gabriel Gugiu; Alyssa Thunen; Keith Le; John E Shively Journal: Obesity (Silver Spring) Date: 2022-07 Impact factor: 9.298