Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 5 Date: 24 Nov 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/
SIRT1 signaling pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin
proved to upregulate the phosphorylation of ErbB3 in MAFLD cells. This study aimed to
investigate the role of NRG1 in the pathogenesis of MAFLD.HepG2 cells were exposed to oleic
acid and palmitic acid to establish a cellular model of MAFLD. MAFLD animal model was
established by feeding C57BL/6J mice with high-fat diet. H&E staining, oil red staining, and
biochemical tests were used to evaluate the models. The results showed that the expressions
of NRG1 in MAFLD cell and animal models were significantly lower than that in the control
group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased
significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1
ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver
injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3,
p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues
of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased.
The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059.The
data above suggest that  NRG1 might play a protective role in the pathogenesis of MAFLD
by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression
of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for
MAFLD.
It is a topic of interest to the researchers in the related areas .Because the authors have revised all
problem I raised, I think the paper should  be considered for publicatio.My detailed comments
are as follows:
1.the introduction ,materials and methods  in the paper work  well ,especially  Animal
experiments,Histological analysis,Tunel staining,Western blotting analysis
, Cell culture and treatments,Cell viability assay, Enzyme-linked immunosorbent assay, and
Intracellular ROS.
2. Results are good and the resolutions of the figures are high,  the part of dicussion has been
well discussed combined with results and references .
3. the references  are  up-to-date now#
Because the authors have revised all problem I raised, I think the paper should  be considered
for publication.
Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 5 Date: 24 Nov 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/
SIRT1 signaling pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin
proved to upregulate the phosphorylation of ErbB3 in MAFLD cells. This study aimed to
investigate the role of NRG1 in the pathogenesis of MAFLD.HepG2 cells were exposed to oleic
acid and palmitic acid to establish a cellular model of MAFLD. MAFLD animal model was
established by feeding C57BL/6J mice with high-fat diet. H&E staining, oil red staining, and
biochemical tests were used to evaluate the models. The results showed that the expressions
of NRG1 in MAFLD cell and animal models were significantly lower than that in the control
group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased
significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1
ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver
injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3,
p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues
of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased.
The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059.The
data above suggest that  NRG1 might play a protective role in the pathogenesis of MAFLD
by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression
of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for
MAFLD.
It is a topic of interest to the researchers in the related areas .Because the authors have revised all
problem I raised, I think the paper should  be considered for publicatio.My detailed comments
are as follows:
1.the introduction ,materials and methods  in the paper work  well ,especially  Animal
experiments,Histological analysis,Tunel staining,Western blotting analysis
, Cell culture and treatments,Cell viability assay, Enzyme-linked immunosorbent assay, and
Intracellular ROS.
2. Results are good and the resolutions of the figures are high,  the part of dicussion has been
well discussed combined with results and references .
3. the references  are  up-to-date now#
Because the authors have revised all problem I raised, I think the paper should  be considered
for publication.
Please review this paper.
user
Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 5 Date: 24 Nov 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/
SIRT1 signaling pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin
proved to upregulate the phosphorylation of ErbB3 in MAFLD cells. This study aimed to
investigate the role of NRG1 in the pathogenesis of MAFLD.HepG2 cells were exposed to oleic
acid and palmitic acid to establish a cellular model of MAFLD. MAFLD animal model was
established by feeding C57BL/6J mice with high-fat diet. H&E staining, oil red staining, and
biochemical tests were used to evaluate the models. The results showed that the expressions
of NRG1 in MAFLD cell and animal models were significantly lower than that in the control
group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased
significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1
ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver
injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3,
p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues
of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased.
The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059.The
data above suggest that  NRG1 might play a protective role in the pathogenesis of MAFLD
by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression
of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for
MAFLD.
It is a topic of interest to the researchers in the related areas .Because the authors have revised all
problem I raised, I think the paper should  be considered for publicatio.My detailed comments
are as follows:
1.the introduction ,materials and methods  in the paper work  well ,especially  Animal
experiments,Histological analysis,Tunel staining,Western blotting analysis
, Cell culture and treatments,Cell viability assay, Enzyme-linked immunosorbent assay, and
Intracellular ROS.
2. Results are good and the resolutions of the figures are high,  the part of dicussion has been
well discussed combined with results and references .
3. the references  are  up-to-date now#
Because the authors have revised all problem I raised, I think the paper should  be considered
for publication.
assistant