title: PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Lepr(db/db) mice.
abstract: PKCδ has been linked to key pathophysiological features of non-alcoholic fatty liver disease (NAFLD). Yet, our knowledge of PKCδ's role in NAFLD development and progression in obese models is limited. PKCδ(-/-)/Lepr(db)(/)(db) mice were generated to evaluate key pathophysiological features of NAFLD in mice. Hepatic histology, oxidative stress, apoptosis, gene expression, insulin signaling, and serum parameters were analyzed in Lepr(db)(/)(db) and PKCδ(-/-)/Lepr(db)(/)(db) mice. The absence of PKCδ did not abrogate the development of obesity in Lepr(db)(/)(db) mice. In contrast, serum triglyceride levels and epididymal white adipose tissue weight normalized to body weight were reduced in PKCδ(-/-)/Lepr(db)(/)(db) mice compared Lepr(db)(/)(db) mice. Analysis of insulin signaling in mice revealed that hepatic Akt and GSK3β phosphorylation were strongly stimulated by insulin in PKCδ(-/-)/Lepr(db)(/)(db) compared Lepr(db)(/)(db) mice. PKCδ may be involved in the development of obesity-associated NAFLD by regulating hepatic lipid metabolism and insulin signaling.
authors.affiliation: Boshell Diabetes and Metabolic Disease Research Program, Auburn University, Auburn, AL 36849, United States; College of Human Sciences, Auburn University, Auburn, AL 36849, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Bassett Research Institute, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Burrington
authors.affiliation: Department of Pathology, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States.
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Davenport
authors.affiliation: Bassett Research Institute, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Johnson
authors.affiliation: Bassett Research Institute, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Horsman
authors.affiliation: Department of Internal Medicine, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States.
authors.forename: Saleem
authors.initials: S
authors.lastname: Chowdhry
authors.affiliation: Boshell Diabetes and Metabolic Disease Research Program, Auburn University, Auburn, AL 36849, United States; College of Human Sciences, Auburn University, Auburn, AL 36849, United States; Bassett Research Institute, Bassett Medical Center, Bassett Healthcare Network, Cooperstown, NY 13326, United States. Electronic address: mwgreene@auburn.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Greene
mesh_terms: D000818:Animals; D001835:Body Weight; D005234:Fatty Liver / Q000378:metabolism; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009929:Organ Size; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D007328:Insulin; D014280:Triglycerides; D051745:Protein Kinase C-delta
keywords: Insulin resistance; Obesity; Oxidative stress; Steatosis