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Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis.
- Source :
-
Nature communications [Nat Commun] 2022 Dec 13; Vol. 13 (1), pp. 7715. Date of Electronic Publication: 2022 Dec 13. - Publication Year :
- 2022
-
Abstract
- A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic 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, 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 Glucose-Regulated Protein78were elevated in patients with non-alcoholic steato-hepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases.<br /> (© 2022. The Author(s).)
- Subjects :
- Rats
Animals
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins metabolism
Insulin metabolism
Diet, High-Fat adverse effects
HSP70 Heat-Shock Proteins metabolism
Liver metabolism
Glucose metabolism
Insulin Resistance genetics
Non-alcoholic Fatty Liver Disease metabolism
Hyperglycemia metabolism
Hepatitis
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 36513656
- Full Text :
- https://doi.org/10.1038/s41467-022-35310-5