SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated, lipid-induced hepatic endoplasmic reticulum stress.

Zheng X, Xu F, Liang H, Cao H, Cai M, Xu W, Weng J

Hepatology (Baltimore, Md.)20 Jul 2017Cited by 67 (Europe PMC)

PMID28439947DOI10.1002/hep.29238PepBankPUB-28439947

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study14

10 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, exenatide inhibited increased hepatic glucose-regulated protein 78 expression.
In plain wordsIn mice fed a high-fat diet, exenatide reduced the increase in a liver stress marker versus saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseGlucose-regulated protein 78 expression
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Normal saline
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated · intraperitoneal · 4 weeksAs given in this study (mouse).
Source sentences
Summary
We observed that HFD feeding induced hepatic ER stress as indicated by increased expression of glucose-regulated protein 78, phosphorylated protein kinase-like ER kinase, and phosphorylated eukaryotic initiation factor 2α, while these increases were significantly inhibited by exenatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
Report a problemFND-2843994701
02AnimalAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, exenatide inhibited increased hepatic phosphorylated protein kinase-like ER kinase expression.
In plain wordsIn mice fed a high-fat diet, exenatide reduced the increase in phosphorylated PERK versus saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePhosphorylated PERK expression
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Normal saline
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated · intraperitoneal · 4 weeksAs given in this study (mouse).
Source sentences
Summary
We observed that HFD feeding induced hepatic ER stress as indicated by increased expression of glucose-regulated protein 78, phosphorylated protein kinase-like ER kinase, and phosphorylated eukaryotic initiation factor 2α, while these increases were significantly inhibited by exenatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
Report a problemFND-2843994702
03AnimalAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, exenatide inhibited increased hepatic phosphorylated eukaryotic initiation factor 2α expression.
In plain wordsIn mice fed a high-fat diet, exenatide reduced the increase in phosphorylated eIF2α versus saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePhosphorylated eIF2α expression
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Normal saline
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated · intraperitoneal · 4 weeksAs given in this study (mouse).
Source sentences
Summary
We observed that HFD feeding induced hepatic ER stress as indicated by increased expression of glucose-regulated protein 78, phosphorylated protein kinase-like ER kinase, and phosphorylated eukaryotic initiation factor 2α, while these increases were significantly inhibited by exenatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
Report a problemFND-2843994703
04AnimalAnimal study (in vivo)Efficacy outcome
In high-fat diet-fed mice, exenatide decreased liver weight versus saline.
In plain wordsIn mice fed a high-fat diet, exenatide decreased liver weight versus saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseLiver weight
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Normal saline
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · intraperitoneal · 4 weeksAs given in this study (mouse).
Source sentences
Summary
Exenatide notably decreased the liver weight and hepatic steatosis induced by HFD challenge.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
Report a problemFND-2843994704
05AnimalAnimal study (in vivo)Efficacy outcome
In high-fat diet-fed mice, exenatide decreased hepatic steatosis versus saline.
In plain wordsIn mice fed a high-fat diet, exenatide decreased liver fat accumulation versus saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHepatic steatosis
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Normal saline
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · intraperitoneal · 4 weeksAs given in this study (mouse).
Source sentences
Summary
Exenatide notably decreased the liver weight and hepatic steatosis induced by HFD challenge.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
Report a problemFND-2843994705
06LabIn vitro (cells)Mechanism
In HepG2 cells and primary murine hepatocytes, exendin‑4 alleviated palmitate-induced ER stress.
In plain wordsIn cells, exendin‑4 reduced stress caused by palmitate.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseER stress
Study
Human and mousen: not reported in source
HepG2 cells and primary murine hepatocytes
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Consistently, in human HepG2 cells and primary murine hepatocytes, exendin-4 also significantly alleviated the ER stress and lipid accumulation induced by palmitate.
Report a problemFND-2843994706
07LabIn vitro (cells)Efficacy outcome
In HepG2 cells and primary murine hepatocytes, exendin‑4 alleviated palmitate-induced lipid accumulation.
In plain wordsIn cells, exendin‑4 reduced fat accumulation caused by palmitate.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseLipid accumulation
Study
Human and mousen: not reported in source
HepG2 cells and primary murine hepatocytes
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Consistently, in human HepG2 cells and primary murine hepatocytes, exendin-4 also significantly alleviated the ER stress and lipid accumulation induced by palmitate.
Report a problemFND-2843994707
08LabOther designMechanism
In mechanistic experiments, exendin‑4 enhanced HSF1 binding to HSP gene promoters through SIRT1-mediated deacetylation.
In plain wordsIn lab tests, exendin‑4 increased binding of HSF1 to heat shock protein gene promoters through SIRT1.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHSF1 binding to HSP promoters
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Importantly, further studies showed that exendin-4 enhanced the binding of heat shock factor 1 to the promoter of heat shock protein (HSP) genes through SIRT1-mediated deacetylation, which then increased the expression of molecular chaperones HSP70 and HSP40 to alleviate hepatic ER stress.
Report a problemFND-2843994708
09LabOther designMechanism
In mechanistic experiments, exendin‑4 increased HSP70 expression through the SIRT1/HSF1 pathway.
In plain wordsIn lab tests, exendin‑4 increased HSP70 expression.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHSP70 expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Importantly, further studies showed that exendin-4 enhanced the binding of heat shock factor 1 to the promoter of heat shock protein (HSP) genes through SIRT1-mediated deacetylation, which then increased the expression of molecular chaperones HSP70 and HSP40 to alleviate hepatic ER stress.
Report a problemFND-2843994709
10LabOther designMechanism
In mechanistic experiments, exendin‑4 increased HSP40 expression through the SIRT1/HSF1 pathway.
In plain wordsIn lab tests, exendin‑4 increased HSP40 expression.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHSP40 expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Importantly, further studies showed that exendin-4 enhanced the binding of heat shock factor 1 to the promoter of heat shock protein (HSP) genes through SIRT1-mediated deacetylation, which then increased the expression of molecular chaperones HSP70 and HSP40 to alleviate hepatic ER stress.
Report a problemFND-2843994710

Studies that did not test the peptide alone4

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

11AnimalNot a test of Exenatide (exendin-4) aloneAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, SIRT1 inhibition diminished exenatide's effect on HSF1 deacetylation.
In plain wordsIn mice fed a high-fat diet, SIRT1 inhibition reduced exenatide's effect on HSF1 deacetylation.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHSF1 deacetylation under SIRT1 inhibition
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Exenatide without SIRT1 inhibition
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Finally, inhibition of SIRT1 by genetic whole-body heterozygous knockout or by lentiviral short hairpin RNA knockdown greatly diminished the effect of exenatide on deacetylating heat shock factor 1, increasing HSP expression and alleviating ER stress and hepatic steatosis in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2843994711
12AnimalNot a test of Exenatide (exendin-4) aloneAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, SIRT1 inhibition diminished exenatide's effect on HSP expression.
In plain wordsIn mice fed a high-fat diet, SIRT1 inhibition reduced exenatide's effect on heat shock protein expression.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHSP expression under SIRT1 inhibition
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Exenatide without SIRT1 inhibition
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Finally, inhibition of SIRT1 by genetic whole-body heterozygous knockout or by lentiviral short hairpin RNA knockdown greatly diminished the effect of exenatide on deacetylating heat shock factor 1, increasing HSP expression and alleviating ER stress and hepatic steatosis in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2843994712
13AnimalNot a test of Exenatide (exendin-4) aloneAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, SIRT1 inhibition diminished exenatide-mediated ER stress relief.
In plain wordsIn mice fed a high-fat diet, SIRT1 inhibition reduced exenatide's relief of liver cell stress.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseER stress under SIRT1 inhibition
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Exenatide without SIRT1 inhibition
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Finally, inhibition of SIRT1 by genetic whole-body heterozygous knockout or by lentiviral short hairpin RNA knockdown greatly diminished the effect of exenatide on deacetylating heat shock factor 1, increasing HSP expression and alleviating ER stress and hepatic steatosis in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2843994713
14AnimalNot a test of Exenatide (exendin-4) aloneAnimal study (in vivo)Mechanism
In high-fat diet-fed mice, SIRT1 inhibition diminished exenatide-mediated relief of hepatic steatosis.
In plain wordsIn mice fed a high-fat diet, SIRT1 inhibition reduced exenatide's effect against liver fat accumulation.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHepatic steatosis under SIRT1 inhibition
Study
mousen: not reported in source
High-fat diet-fed C57BL/6J mice
Comparator
Exenatide without SIRT1 inhibition
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Finally, inhibition of SIRT1 by genetic whole-body heterozygous knockout or by lentiviral short hairpin RNA knockdown greatly diminished the effect of exenatide on deacetylating heat shock factor 1, increasing HSP expression and alleviating ER stress and hepatic steatosis in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice challenged with a high-fat diet (HFD) were treated with exenatide or normal saline by intraperitoneal injection for 4 weeks.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2843994714

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.