Reviewer's report
Title:Deficiency of Endothelial Nitric Oxide Synthase Exacerbates Early-stage
Non-Alcoholic Fatty Liver Disease Pathogenesis by Changing the Fat Distribution
Version:1Date:31 August 2015
Reviewer: Syeda Afroze
Reviewer's report:
In this manuscript entitled “Deficiency of Endothelial Nitric Oxide Synthase
Exacerbates Early-stage Non-Alcoholic Fatty Liver Disease Pathogenesis by
Changing the Fat Distribution” submitted by Nozaki et al, the authors aimed to
demonstrate the role of endothelial nitric oxide synthase (eNOS) derived nitric
oxide (NO) in the pathogenesis od NAFLD / NASH. There are several factors or
molecules are responsible for the pathogenesis of non-alcoholic fatty liver
disease (NAFLD) or non-alcoholic steatohepatitis (NASH), but the role of eNOS
derived NO in the pathogenesis of NAFLD / NASH is not yet well defined.
Therefore to investigate their hypothesis authors performed experiments in
systemic eNOS-knockout mice with high-fat diet. Four groups of mice were used
in this study. Those mice were (a) wild type eNOS+/+ with basal diet (BD), (b)
wild type eNOS-/- with basal diet (BD), (c) wild type eNOS+/+ with High fed Diet
(HFD), (d) wild type eNOS-/- with High fed Diet (HFD). To explore this study the
authors performed measurement of different biochemical markers in plasma and
serum, liver triglyceride content, liver/spleen ratio of CT values and visceral fat
volume as well. The authors determined the insulin tolerance test (ITT), liver
MTP activity assay and hepatic tissue blood flow. CT scan has also been
performed. The authors conducted several experiments as well, like as
histopathological study on liver and immunohistochemical study as well. The
authors also performed qPCR for evaluating at these genes expressions
(SREBP-1c, PPAR-#, nNOS, iNOS). It is an interesting study. As a whole the
expression of this manuscript is well described. So before going for final
submission of this manuscript, it is recommended to take care of this manuscript
in terms of the following minor revision. Minor concerns are mentioned below:
Minor Concerns:
1. The manuscript should be carefully checked and need to follow the manuscript
format criteria for this journal.
2. It is good to revise by Scientific English editor.
3. The Title could be more firm such as “Deficiency of eNOS Exacerbates
Early-stage NAFLD Pathogenesis by Changing the Fat Distribution”
4. Materials and Methods section need to be organized in order of experiment,
for an example all the measurements need to be one after another then all the
assays and then histological study and then qPCR (gene expression study).
5. Figure 4-1 is not clear enough, because all the lines for different groups are
overlapped. Even though the error bar as well. So it is good to use different color
line for each group. So the figure should be clearly visible. Or the figure could be
represented by bar graph either way.
Reviewer's report
Title:Deficiency of Endothelial Nitric Oxide Synthase Exacerbates Early-stage
Non-Alcoholic Fatty Liver Disease Pathogenesis by Changing the Fat Distribution
Version:1Date:31 August 2015
Reviewer: Syeda Afroze
Reviewer's report:
In this manuscript entitled “Deficiency of Endothelial Nitric Oxide Synthase
Exacerbates Early-stage Non-Alcoholic Fatty Liver Disease Pathogenesis by
Changing the Fat Distribution” submitted by Nozaki et al, the authors aimed to
demonstrate the role of endothelial nitric oxide synthase (eNOS) derived nitric
oxide (NO) in the pathogenesis od NAFLD / NASH. There are several factors or
molecules are responsible for the pathogenesis of non-alcoholic fatty liver
disease (NAFLD) or non-alcoholic steatohepatitis (NASH), but the role of eNOS
derived NO in the pathogenesis of NAFLD / NASH is not yet well defined.
Therefore to investigate their hypothesis authors performed experiments in
systemic eNOS-knockout mice with high-fat diet. Four groups of mice were used
in this study. Those mice were (a) wild type eNOS+/+ with basal diet (BD), (b)
wild type eNOS-/- with basal diet (BD), (c) wild type eNOS+/+ with High fed Diet
(HFD), (d) wild type eNOS-/- with High fed Diet (HFD). To explore this study the
authors performed measurement of different biochemical markers in plasma and
serum, liver triglyceride content, liver/spleen ratio of CT values and visceral fat
volume as well. The authors determined the insulin tolerance test (ITT), liver
MTP activity assay and hepatic tissue blood flow. CT scan has also been
performed. The authors conducted several experiments as well, like as
histopathological study on liver and immunohistochemical study as well. The
authors also performed qPCR for evaluating at these genes expressions
(SREBP-1c, PPAR-#, nNOS, iNOS). It is an interesting study. As a whole the
expression of this manuscript is well described. So before going for final
submission of this manuscript, it is recommended to take care of this manuscript
in terms of the following minor revision. Minor concerns are mentioned below:
Minor Concerns:
1. The manuscript should be carefully checked and need to follow the manuscript
format criteria for this journal.
2. It is good to revise by Scientific English editor.
3. The Title could be more firm such as “Deficiency of eNOS Exacerbates
Early-stage NAFLD Pathogenesis by Changing the Fat Distribution”
4. Materials and Methods section need to be organized in order of experiment,
for an example all the measurements need to be one after another then all the
assays and then histological study and then qPCR (gene expression study).
5. Figure 4-1 is not clear enough, because all the lines for different groups are
overlapped. Even though the error bar as well. So it is good to use different color
line for each group. So the figure should be clearly visible. Or the figure could be
represented by bar graph either way.
Please review this paper.
user
Reviewer's report
Title:Deficiency of Endothelial Nitric Oxide Synthase Exacerbates Early-stage
Non-Alcoholic Fatty Liver Disease Pathogenesis by Changing the Fat Distribution
Version:1Date:31 August 2015
Reviewer: Syeda Afroze
Reviewer's report:
In this manuscript entitled “Deficiency of Endothelial Nitric Oxide Synthase
Exacerbates Early-stage Non-Alcoholic Fatty Liver Disease Pathogenesis by
Changing the Fat Distribution” submitted by Nozaki et al, the authors aimed to
demonstrate the role of endothelial nitric oxide synthase (eNOS) derived nitric
oxide (NO) in the pathogenesis od NAFLD / NASH. There are several factors or
molecules are responsible for the pathogenesis of non-alcoholic fatty liver
disease (NAFLD) or non-alcoholic steatohepatitis (NASH), but the role of eNOS
derived NO in the pathogenesis of NAFLD / NASH is not yet well defined.
Therefore to investigate their hypothesis authors performed experiments in
systemic eNOS-knockout mice with high-fat diet. Four groups of mice were used
in this study. Those mice were (a) wild type eNOS+/+ with basal diet (BD), (b)
wild type eNOS-/- with basal diet (BD), (c) wild type eNOS+/+ with High fed Diet
(HFD), (d) wild type eNOS-/- with High fed Diet (HFD). To explore this study the
authors performed measurement of different biochemical markers in plasma and
serum, liver triglyceride content, liver/spleen ratio of CT values and visceral fat
volume as well. The authors determined the insulin tolerance test (ITT), liver
MTP activity assay and hepatic tissue blood flow. CT scan has also been
performed. The authors conducted several experiments as well, like as
histopathological study on liver and immunohistochemical study as well. The
authors also performed qPCR for evaluating at these genes expressions
(SREBP-1c, PPAR-#, nNOS, iNOS). It is an interesting study. As a whole the
expression of this manuscript is well described. So before going for final
submission of this manuscript, it is recommended to take care of this manuscript
in terms of the following minor revision. Minor concerns are mentioned below:
Minor Concerns:
1. The manuscript should be carefully checked and need to follow the manuscript
format criteria for this journal.
2. It is good to revise by Scientific English editor.
3. The Title could be more firm such as “Deficiency of eNOS Exacerbates
Early-stage NAFLD Pathogenesis by Changing the Fat Distribution”
4. Materials and Methods section need to be organized in order of experiment,
for an example all the measurements need to be one after another then all the
assays and then histological study and then qPCR (gene expression study).
5. Figure 4-1 is not clear enough, because all the lines for different groups are
overlapped. Even though the error bar as well. So it is good to use different color
line for each group. So the figure should be clearly visible. Or the figure could be
represented by bar graph either way.
assistant