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:22 May 2014
Reviewer: ALEXANDER WREE
Reviewer's report:
Reviewer’s comment:
The manuscript by Duan et al. report a benefical effect of feeding with
high-saturate-fat diet (HFD) in mice treated with the hepatocarcinogen
diethylnitrosamine (DEN). They report the development of liver cirrhosis and
hepatic tumors accompanied by a decrease in body weight in mice fed with
normal control diet (NCD) and DEN treatment. Mice fed with HFD developed
hepatic steatosis, showed attenuated malnutrition and liver fibrosis. Tumors in
the liver were found to be smaller and less frequent in HFD mice when compared
to NCD mice treated with DEN. The results are reported in a clear and
well-organized manner. The article is well written and easily understandable.
Major comments
• The abstract provided does not give any background and introduction to the
topic. The sentence given with the heading background describes the aim of the
study. Moreover, authors introduce the abbreviation DNE for diethylnitrosamine.
• Based on which rationale did the authors chose the time points 10, 12, and 14
weeks? DEN has been used for a broad range of time points in rats anywhere
from 8 weeks to 16 months (e.g. Taya et al 2014, Carthew et al 1997, Takahashi
et al. 1984).
• Authors extensively describe the liver histology in mice fed with NCD and HFD
with or without DEN treatment. Therefore, macroscopic images of livers should
be presented in Figure 1 along with microphotographs in high, as well as in low
magnifications.
• Did the authors perform any specific staining to assess liver fibrosis, e.g. Sirius
Red Staining or Masson's trichrome? If so, this should be presented to the
readership.
• Authors state in the Method section that a commercial enzyme-linked
immunosorbent assay (ELISA) kit was used to quantify the active form of
Caspase 3. However, in the Results, as well as the Figures, they report the total
content of Caspase 3. Authors emphasize the resistance to apoptoic cell death
as an important contributor to the documented phenotype. How do authors
explain that the hepatic content of Caspase 3 is increased in measurements at
week 10 and 12, while decreased at 14 weeks in the HFD+DEN group when
compared to the NCD+DEN group?
• In previous studies, DEN has been administered via gavage, peritoneal
injection, or tail vein injection. The main effect reported in the presented study is
addressed to a dietary intervention. How can the authors exclude that the diet
itself does not interfere with the DEN? Is the beneifical effect of HFD still present
when DEN is administered via a non-oral path?
Minor comments and errata
Page 5, line 1: “Metavir Score system”. An appropriate reference should be
added.
Page 6, line 10: “ as shown in Table 4”, do the authors mean Table 1 or do they
refer to additional table.
Figure 2: Number of mice per group analysed in panel B and C should be given.
Figure 3: Number of mice per group analysed in the panel should be given.
In principle, the proposed role of high fat diet for hepatocarcinogenesis is novel
and interesting. However, the manuscript in the current forms is descriptive and
does not provide convincing mechanistic support of the reported findings.
Therefore, with the suggested major revisions regarding experiments and
discussion, the manuscript by Duan et al. may be re-submitted for publication in
BMC Gastroenterology. Without additional clarification and major changes to the
manuscript I would advise against publication in the presented form.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests