The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

By R. Perry, V. Samuel, K. Petersen, Gerald I. Shulman. Nature, 2014

1,068 citations recorded by the source corpus.

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Surgery

View Paper: https://www.semanticscholar.org/paper/4666a5312d864410db8f1b867279749c8a9fd050

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

1. Christopher D. Byrne
2. G. Targher
3. G. Svegliati-Baroni
4. Amirhossein Sahebkar
5. Jeremy K. Nicholson
6. F. Marra
7. Habib Yaribeygi
8. A. Chait

In Epidemiology

1. Christopher D. Byrne
2. G. Targher
3. Jamal Naderi
4. P. Tveden‐Nyborg
5. G. Svegliati-Baroni
6. M. Longo
7. C. Miele
8. F. Marra

In Surgery

1. G. Svegliati-Baroni
2. Christopher D. Byrne
3. F. Marra
4. A. Chait
5. G. Targher
6. Laura J. den Hartigh

Citations in the corpus

• Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications (2019, background): “Convergent evidence suggests a role in lipid-induced hepatic IR for these intermediate lipid products [146,147].”
• Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease (2020, background): “, DAGs and ceramide) have been shown to promote lipotoxicity and enhance hepatic insulin resistance (296), likely by inhibiting insulin signaling pathways (297, 298).”
• Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease (2018, background): “Diacylglycerides are precursors of triglycerides, and hepatic accumulation of diacylglycerides has been associated with hepatic insulin resistance through the induction of protein kinase Cε [68].”
• Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “ceramides) may modulate metabolic and inflammatory pathways [7].”
• Insulin resistance: Review of the underlying molecular mechanisms (2018, background): “IR is inversely correlated to insulin sensitivity in insulin‐dependent tissues and disables their ability to take up and utilize glucose, the preferred metabolic substrate (Perry et al., 2014).”
• NAFLD: a multisystem disease. (2015, background): “Journal of Hepatology 201 products (particularly DAGs) is very important in causing ‘resistance’ within the hepatic insulin signaling pathway [61], promoting hepatic inflammation [62–65] and increasing risk of progressive liver disease that occurs with NASH.”
• Impact of the gut microbiota on inflammation, obesity, and metabolic disease (2016, background): “Insulin also reduces degradation and recirculation of carbohydrates and lipids by inhibiting gluconeogenesis and lipolysis [19, 20].”