Evan H. Nicklas
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Evan H. Nicklas has a total of 13 co-authors. Here are the top co-authors by number of shared publications:
- Albert Tran
Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
1 shared publication - Arlan Richardson
Department of Biochemistry and Physiology, University of Oklahoma Health Campus, Oklahoma City, OK USA
1 shared publication - Dawei Wang
Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
1 shared publication - Hoang Van M. Nguyen
Department of Biochemistry and Physiology, College of Medicine University of Oklahoma Health Sciences Oklahoma City Oklahoma USA
1 shared publication - Jacob W. Farriester
Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
1 shared publication - Michael C. Rudolph
Department of Biochemistry and Physiology, Harold Hamm Diabetes Center Oklahoma University Health Science Center Oklahoma City OK USA
1 shared publication
Latest Publications
- Open Access
- 28 February 2024
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 25 (5) , 2813
Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model
Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to the diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain-like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD. Despite the HFHFrHC diet upregulating MLKL (2.5-fold), WT mice livers showed no increase in necroptosis markers or associated proinflammatory cytokines. Surprisingly, Mlkl−/− mice experienced exacerbated liver inflammation without protection from diet-induced liver damage, steatosis, or fibrosis. In contrast, Mlkl+/− mice showed a significant reduction in these parameters that was associated with elevated Pparα and Pparγ levels. Both Mlkl−/− and Mlkl+/− mice on the HFHFrHC diet resisted diet-induced obesity, attributed to the increased beiging, enhanced oxygen consumption, and energy expenditure due to adipose tissue, and exhibited improved insulin sensitivity. These findings highlight the tissue-specific effects of MLKL on the liver and adipose tissue, and they suggest a dose-dependent effect of MLKL on liver pathology.
- 28 February 2024
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 25 (5) , 2813
Open AccessNon-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model
Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to the diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain-like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD. Despite the HFHFrHC diet upregulating MLKL (2.5-fold), WT mice livers showed no increase in necroptosis markers or associated proinflammatory cytokines. Surprisingly, Mlkl−/− mice experienced exacerbated liver inflammation without protection from diet-induced liver damage, steatosis, or fibrosis. In contrast, Mlkl+/− mice showed a significant reduction in these parameters that was associated with elevated Pparα and Pparγ levels. Both Mlkl−/− and Mlkl+/− mice on the HFHFrHC diet resisted diet-induced obesity, attributed to the increased beiging, enhanced oxygen consumption, and energy expenditure due to adipose tissue, and exhibited improved insulin sensitivity. These findings highlight the tissue-specific effects of MLKL on the liver and adipose tissue, and they suggest a dose-dependent effect of MLKL on liver pathology.