Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy

Frontiers in Pharmacology
Zhi-Ming DingHaiqing Hua

Abstract

Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods. Male C57BL/6 mice fed Western diet developed progressive hepatic steatosis/macrovesicular vacuolation, inflammation, and hepatocyte degeneration, as well as perisinusoidal fibrosis and occasionally portal fibrosis as early as 2 months after initiation of the Western diet. In the same period, the mice exhibited elevated ALT (alanine aminotransferase) and AST (aspartate aminotransferase) enzyme activities, CK18 (cytokeratin-18), PIIINP (N-terminal propeptide of type III collagen), and TIMP-1 (tissue inhibitor of metalloproteinase-1). Hepatic steatosis diminished rapidly when the Western diet was r...Continue Reading

References

Sep 14, 1999·The American Journal of Gastroenterology·E M BruntB R Bacon
Apr 2, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giulio MarchesiniMario Rizzetto
Dec 4, 2004·Gastroenterology·William M C RosenbergUNKNOWN European Liver Fibrosis Group
May 3, 2005·The Journal of Clinical Investigation·Kerry L DonnellyElizabeth J Parks
May 17, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giorgio BedogniStefano Bellentani
Oct 20, 2005·American Journal of Physiology. Renal Physiology·Takahiko NakagawaRichard J Johnson
Apr 25, 2006·Liver International : Official Journal of the International Association for the Study of the Liver·Monika van ZonneveldUNKNOWN HBV 99-01 Study Group
Oct 29, 2008·Seminars in Liver Disease·Onpan Cheung, Arun J Sanyal
Dec 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sarah L GeorgeAdrian M Di Bisceglie
Oct 13, 2009·Clinics in Liver Disease·Elizabeth M Brunt
Oct 15, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kittichai PromratRena R Wing
Mar 16, 2012·Seminars in Liver Disease·David E Kleiner, Elizabeth M Brunt
Feb 19, 2013·Journal of Lipid Research·George N IoannouChristopher Savard
Jul 28, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jason R ClapperJonathan D Roth
Apr 29, 2014·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Siddharth SinghRohit Loomba
Apr 14, 2015·Gastroenterology·Eduardo Vilar-GomezManuel Romero-Gomez
Jan 26, 2016·Metabolism: Clinical and Experimental·Suzanne E Mahady, Jacob George
Apr 12, 2016·Clinics in Liver Disease·David E Kleiner, Hala R Makhlouf
Apr 12, 2016·Clinics in Liver Disease·Andrea MarengoElisabetta Bugianesi
May 24, 2016·International Journal of Molecular Sciences·Luis Calzadilla Bertot, Leon Anton Adams
Oct 16, 2016·Clinics in Liver Disease·Don C Rockey

❮ Previous
Next ❯

Citations

Jan 26, 2020·Scientific Reports·Helene M ÆgidiusKristoffer T G Rigbolt
Sep 24, 2019·World Journal of Gastroenterology : WJG·Michelle L BolandHenrik H Hansen
Jul 8, 2020·BMC Gastroenterology·Henrik H HansenKristoffer T G Rigbolt
Aug 20, 2019·The Journal of Pharmacology and Experimental Therapeutics·Daxesh P PatelFrank J Gonzalez
Aug 27, 2019·International Immunopharmacology·Xiaohui WangQiang Meng
Feb 6, 2021·Hepatology International·Sonia SeliceanJordi Gracia-Sancho

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
ELISA
Assay
pharmacotherapy

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.