The DOI matches its Crossref record; 62 of the 64 references it cites were found in a registry or an index.
Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice
Open accessAbstract
In order to investigate the role of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) in the pathogenesis of hepatic steatosis and hepatic insulin resistance, we examined whole-body insulin action in awake mtGPAT1 knockout (mtGPAT1(-/-)) and wild-type (wt) mice after regular control diet or three weeks of high-fat feeding. In contrast to high-fat-fed wt mice, mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations and were protected from hepatic insulin resistance possibly due to a lower diacylglycerol-mediated PKC activation. Hepatic acyl-CoA has previously been implicated in the pathogenesis of insulin resistance. Surprisingly, compared to wt mice, mtGPAT1(-/-) mice exhibited increased hepatic insulin sensitivity despite an almost 2-fold elevation in hepatic acyl-CoA content. These data suggest that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance and that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model.
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In the citing paper
“recent studies have demonstrated that NAFLD-induced hepatic insulin resistance is a major factor responsible for the transition from normoglycemia to fasting hyperglycemia and T2DM (18–23).”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [22]
In the citing paper
“NAFLD is strongly linked to hepatic insulin resistance”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [22]
In the citing paper
“In this setting, PKCε, but not other isoforms of PKC, is activated.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“An alternate hypothesis is that the development of hepatic steatosis per se causes hepatic insulin resistance.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“Preventing fat accumulation in rodents preserves hepatic insulin action (7,10,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“Preventing fat accumulation by inhibiting lipid synthesis via disruption of the mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase (7) or promoting fat oxidation using either the mitochondrial uncoupler 2,4-dinitrophenol (10) or inhibition of acetyl-CoA carboxylase-1 and -2 (12) prevents PKCε activation and hepatic insulin resistance.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“This is important since DAG is a known activator of classic and novel isoforms of PKC and DAG concentrations have closely paralleled insulin resistance in other models (7,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“This is important since DAG is a known activator of classic and novel isoforms of PKC and DAG concentrations have closely paralleled insulin resistance in other models (7,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
In the citing paper
“There is increasing evidence for a causal relationship between hepatic steatosis and hepatic insulin resistance both in rodent models with hepatic steatosis and in patients with nonalcoholic fatty liver disease (4, 18-25).”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [22]
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Metadata
- Authors
- Neschen, S., Morino, K., Hammond, L. E., Zhang, D., Liu, Z.-X., Romanelli, A. J., Cline, G. W., Pongratz, R. L., Zhang, X.-M., Choi, C. S., Coleman, R. A., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of North Carolina at Chapel Hill (US)
- Yale University (US)
- Corresponding author
- Shulman, Gerald I.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 2
- Issue
- 1
- Pages
- 55-65
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2006375647
- Semantic Scholar
- e7251c54287df4fd1cb668ac0f825e2c909f61c2
- Cited by
- 261
- References
- 64
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 4 · 2015: 12 · 2014: 16 · 2013: 13 · 2012: 20
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (F31GM020920, F31 GM20920)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK40936, R01DK56598, U24DK59635, R01DK040936, U24DK059635, R01DK056598)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- hepatic steatosis, hepatic insulin resistance, knockout mice, high-fat diet, diacylglycerol, protein kinase C, triglycerides, insulin sensitivity, lipid metabolism
- MeSH terms
- Acetyl-CoA Carboxylase, Acetyl Coenzyme A, Animals, Dietary Fats, Diglycerides, Fasting, Fatty Liver, Glucose Tolerance Test, Glycerol-3-Phosphate O-Acyltransferase, Insulin Resistance, Liver, Lysophospholipids, Male, Malonyl Coenzyme A, Mice, Inbred C57BL, Mitochondria, Multienzyme Complexes, Phenotype, Triglycerides, Protein Serine-Threonine Kinases, Mice, Knockout, Mice, AMP-Activated Protein Kinases
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