Review for 10.1186/s12876-014-0195-9 (2014)

Reviewer's report
Title:High-saturate-fat diet delays development of diethylnitrosamine-induced
hepatocellular carcinoma
Version:3Date:31 May 2014
Reviewer: Steven Dooley
Reviewer's report:
Major Compulsory Revisions
The author must respond to these before a decision on publication can be
reached. For example, additional necessary experiments or controls, statistical
mistakes, errors in interpretation.
Authors showed that high fat diet can delay HCC development in a rat DEN
model. The finding is very interesting and important for HCC research. The
current finding is contrary to the finding from Hill-Baskin AE et al, Hum Mol
Genet. 2009. Park EJ et al Cell. 2010 , Blanche C. Ip et al. The Journal of
Nutrition. 2014. However, different models were used. In this paper, authors used
a rat DEN HCC model as contrasting with mice DEN HCC models in the other
above mentioned papers. Further, a different genetic background might cause
different responses to high fat diet. But, still several major concerns are relevant.
These papers should be carefully discussed in the context of the authors results.
1. In the current paper, the authors showed that high fat diet can delay HCC.
However, the low fat diet group should also be included, to see whether low fat
diet could promote HCC. This will be a valuable information to understand how
fat diet can affect HCC development in rats.
2. Authors showed reduced proliferation and increased apoptosis in high fat diet
DEN mice at 10 and 12 weeks. Here, more molecular details should be
addressed to find out the mechanism behind the observation. In figure 3, at week
14, apoptosis rates in high fat diet DEN mice is reduced instead of decreased.
This should be clarified.
3. In figure 1, pictures of the whole liver should be provided to show the
difference.
4. In figure 2a, data from all individual mice should be shown as immunoblot for
PCNA.
5. In figure2a and 3, immunohistochemistry staining of PCNA and Caspase 3
should be shown in order to find out the cell type and expression area in the
animals. Proliferation markers such as ki67 or Tunel staining should also be
provided.
6. In tables 2 and 3, representative photos of fibrosis and differentiation should
be included. Furthermore, inflammation should also be analyzed. Park EJ et al
Cell. 2010 showed that enhanced production of IL-6 and TNF is import for high
fat diet induced HCC in mice. Here, the authors should find out whether the
situation is different in rats and include mRNA/ELISA data for IL6 and TNFa.
7. How many animals were used per time point in each of the analyses? This
should always be stated in the figures.
Minor Essential Revisions
The author can be trusted to make these. For example, missing labels on figures,
the wrong use of a term, spelling mistakes.
1. In figure2a, molecular weight of PCNA and actin should be mentioned on the
picture.
2. In figure 2b, 2c and 3, dot graph would be better than column to show
individual animals.
3. Reference 19 and 33 is exactly the same.
19. Rahman KM, Sugie S, Tanaka T et al. Effect of types and amount of dietary
fat during the
13
initiation phase of hepatocarcinogenesis. Nutr Cancer 2001; 39:220-5.
33. Rahman KM, Sugie S, Tanaka T et al. Effect of types and amount of dietary
fat during the
initiation phase of hepatocarcinogenesis. Nutr Cancer 2001; 39: 220-5.
Discretionary Revisions
These are recommendations for improvement which the author can choose to
ignore. For example clarifications, data that would be useful but not essential.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests