Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis
| Autor: | Angelini, Giulia, Castagneto-Gissey, Lidia, Salinari, Serenella, Bertuzzi, Alessandro, Anello, Danila, Pradhan, Meenakshi, Zschätzsch, Marlen, Ritter, Paul, Le Roux, Carel W, Rubino, Francesco, Basso, Nicola, Casella, Giovanni, Bornstein, Stefan R, Tremaroli, Valentina, Mingrone, Geltrude |
|---|---|
| Přispěvatelé: | University of Zurich, Mingrone, Geltrude |
| Rok vydání: | 2022 |
| Předmět: |
1000 Multidisciplinary
Multidisciplinary Settore MED/09 - MEDICINA INTERNA 10265 Clinic for Endocrinology and Diabetology General Physics and Astronomy 610 Medicine & health 1600 General Chemistry General Chemistry 3100 General Physics and Astronomy General Biochemistry Genetics and Molecular Biology 1300 General Biochemistry Genetics and Molecular Biology insulin resistance non-alcoholic steatohepatitis hyperglycemia shock proteins |
| Popis: | A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and nonalcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat- Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-body insulin-resistance, as well as the metabolic response to bariatric/metabolic surgery. Long-term continuous infusion of Heat-Shock-Protein70 and Glucose-Regulated Protein78 caused insulin-resistance, hyperglycemia, and non-alcoholic steato-hepatitis in rats on a chow diet, while in rats on a high-fat diet continuous infusion of monoclonal antibodies reversed these phenotypes, mimickingmetabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and Glucose- Regulated Protein78were elevated in patients with non-alcoholic steatohepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|