Reviewer's report
Title:Expression of NALPs in adipose and the fibrotic progression of NAFLD in
obese subjects
Version:1Date:25 August 2014
Reviewer: ALEXANDER WREE
Reviewer's report:
Reviewer’s comment:
The manuscript by Metha et al. describes the results of visceral adipose
expression analysis of various NALPs and downstream effectors caspase-1,
ASC and IL-1# in obese subjects with biopsy proven NAFLD. They report
reduced expression levels of several NALPs in adipose tissue in patients with
non-NASH NAFLD when compared to features of liver histology in patients with
NASH. In analysing circulating IL18 levels authors report an association with
increased liver injury markers (ALT, AST) and portal liver fibrosis. In principle, the
findings gathered in a large human study (N=45) with a reasonable proportion of
NASH patients (N=20) are interesting. However, in the current form the concept
of the manuscript is not sufficiently supported by the presented data. In addition,
as pointed out in the following, there is also some concern with regard to the
design of the study and some technical issue.
Major comments
• Inclusion and exclusion criteria should be clearly defined. Apart from excess
alcohol consumption, were other causes of secondary fatty liver excluded? If not,
this is a definite limitation of the study.
• Expression of NALPs, especially of those with known importance in human
diseases, is preferentially found in cells of the innate immune system.
Independent analysis of isolated adipocytes and infiltrating cells, as done by
Gesta et al. (PNAS, Vol. 103, 6676-6681, 2016), could overcome this issue.
• As pointed out by the authors in the introduction, “…a large number of recent
studies have shown adipose tissue to be the major source of inflammatory…”. It
is therefore crucial to measure inflammation of the adipose tissue and correlate
these readouts to the expression of NALPs and liver injury.
• Throughout the manuscript authors correlate mRNA expression levels of the
adipose tissue to histological changes in the liver. In order to support some
speculations made by the authors in the discussion and conclusion, assessment
of histological changes in the adipose tissue, as well as analysis of NALP
expression levels in the liver, would be very important.
• Authors description of liver histology is very wordy - one page in the submitted
manuscript. Therefore microphotographs of livers should be presented as the
readership might expect those at this point
• Authors focus on mRNA expression analysis of the adipose tissue and
quantification of serum interleukin levels. However, activity of inflammasomes
should be quantified by protein quantification of Casp1 fragment within the tissue
of interest.
Minor comments and errata
References: 28 and 37 are identical
28. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
37. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
Table 1: SI units are missing for multiple variables. It is not clear if “Presences”
refers to an absolute number or a percentage.
Expression analysis of NALP 1, 2, and 3 are mentioned in the Method section but
results are not presented.
With the suggested revisions the manuscript by Metha et al. may be re-submitted
for publication in BMC Gastroenterology. Without these changes to the
manuscript I would advise against publication in the presented form.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Expression of NALPs in adipose and the fibrotic progression of NAFLD in
obese subjects
Version:1Date:25 August 2014
Reviewer: ALEXANDER WREE
Reviewer's report:
Reviewer’s comment:
The manuscript by Metha et al. describes the results of visceral adipose
expression analysis of various NALPs and downstream effectors caspase-1,
ASC and IL-1# in obese subjects with biopsy proven NAFLD. They report
reduced expression levels of several NALPs in adipose tissue in patients with
non-NASH NAFLD when compared to features of liver histology in patients with
NASH. In analysing circulating IL18 levels authors report an association with
increased liver injury markers (ALT, AST) and portal liver fibrosis. In principle, the
findings gathered in a large human study (N=45) with a reasonable proportion of
NASH patients (N=20) are interesting. However, in the current form the concept
of the manuscript is not sufficiently supported by the presented data. In addition,
as pointed out in the following, there is also some concern with regard to the
design of the study and some technical issue.
Major comments
• Inclusion and exclusion criteria should be clearly defined. Apart from excess
alcohol consumption, were other causes of secondary fatty liver excluded? If not,
this is a definite limitation of the study.
• Expression of NALPs, especially of those with known importance in human
diseases, is preferentially found in cells of the innate immune system.
Independent analysis of isolated adipocytes and infiltrating cells, as done by
Gesta et al. (PNAS, Vol. 103, 6676-6681, 2016), could overcome this issue.
• As pointed out by the authors in the introduction, “…a large number of recent
studies have shown adipose tissue to be the major source of inflammatory…”. It
is therefore crucial to measure inflammation of the adipose tissue and correlate
these readouts to the expression of NALPs and liver injury.
• Throughout the manuscript authors correlate mRNA expression levels of the
adipose tissue to histological changes in the liver. In order to support some
speculations made by the authors in the discussion and conclusion, assessment
of histological changes in the adipose tissue, as well as analysis of NALP
expression levels in the liver, would be very important.
• Authors description of liver histology is very wordy - one page in the submitted
manuscript. Therefore microphotographs of livers should be presented as the
readership might expect those at this point
• Authors focus on mRNA expression analysis of the adipose tissue and
quantification of serum interleukin levels. However, activity of inflammasomes
should be quantified by protein quantification of Casp1 fragment within the tissue
of interest.
Minor comments and errata
References: 28 and 37 are identical
28. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
37. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
Table 1: SI units are missing for multiple variables. It is not clear if “Presences”
refers to an absolute number or a percentage.
Expression analysis of NALP 1, 2, and 3 are mentioned in the Method section but
results are not presented.
With the suggested revisions the manuscript by Metha et al. may be re-submitted
for publication in BMC Gastroenterology. Without these changes to the
manuscript I would advise against publication in the presented form.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Expression of NALPs in adipose and the fibrotic progression of NAFLD in
obese subjects
Version:1Date:25 August 2014
Reviewer: ALEXANDER WREE
Reviewer's report:
Reviewer’s comment:
The manuscript by Metha et al. describes the results of visceral adipose
expression analysis of various NALPs and downstream effectors caspase-1,
ASC and IL-1# in obese subjects with biopsy proven NAFLD. They report
reduced expression levels of several NALPs in adipose tissue in patients with
non-NASH NAFLD when compared to features of liver histology in patients with
NASH. In analysing circulating IL18 levels authors report an association with
increased liver injury markers (ALT, AST) and portal liver fibrosis. In principle, the
findings gathered in a large human study (N=45) with a reasonable proportion of
NASH patients (N=20) are interesting. However, in the current form the concept
of the manuscript is not sufficiently supported by the presented data. In addition,
as pointed out in the following, there is also some concern with regard to the
design of the study and some technical issue.
Major comments
• Inclusion and exclusion criteria should be clearly defined. Apart from excess
alcohol consumption, were other causes of secondary fatty liver excluded? If not,
this is a definite limitation of the study.
• Expression of NALPs, especially of those with known importance in human
diseases, is preferentially found in cells of the innate immune system.
Independent analysis of isolated adipocytes and infiltrating cells, as done by
Gesta et al. (PNAS, Vol. 103, 6676-6681, 2016), could overcome this issue.
• As pointed out by the authors in the introduction, “…a large number of recent
studies have shown adipose tissue to be the major source of inflammatory…”. It
is therefore crucial to measure inflammation of the adipose tissue and correlate
these readouts to the expression of NALPs and liver injury.
• Throughout the manuscript authors correlate mRNA expression levels of the
adipose tissue to histological changes in the liver. In order to support some
speculations made by the authors in the discussion and conclusion, assessment
of histological changes in the adipose tissue, as well as analysis of NALP
expression levels in the liver, would be very important.
• Authors description of liver histology is very wordy - one page in the submitted
manuscript. Therefore microphotographs of livers should be presented as the
readership might expect those at this point
• Authors focus on mRNA expression analysis of the adipose tissue and
quantification of serum interleukin levels. However, activity of inflammasomes
should be quantified by protein quantification of Casp1 fragment within the tissue
of interest.
Minor comments and errata
References: 28 and 37 are identical
28. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
37. Szabo G, Csak T: Inflammasomes in liver diseases. Journal of Hepatology
2012, 57:642–654.
Table 1: SI units are missing for multiple variables. It is not clear if “Presences”
refers to an absolute number or a percentage.
Expression analysis of NALP 1, 2, and 3 are mentioned in the Method section but
results are not presented.
With the suggested revisions the manuscript by Metha et al. may be re-submitted
for publication in BMC Gastroenterology. Without these changes to the
manuscript I would advise against publication in the presented form.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
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