A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and nonalcoholic steato-hepatitis. Here we identified two heat-shock proteins, HeatShock-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, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and GlucoseRegulated 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.

Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:(2022). [10.1038/s41467-022-35310-5]

Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis

Lidia Castagneto-Gissey;Serenella Salinari;Nicola Basso;Giovanni Casella;
2022

Abstract

A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and nonalcoholic steato-hepatitis. Here we identified two heat-shock proteins, HeatShock-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, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and GlucoseRegulated 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.
2022
gut; bariatric surgery; incretins
01 Pubblicazione su rivista::01a Articolo in rivista
Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:(2022). [10.1038/s41467-022-35310-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1664431
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