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:24 December 2013
Reviewer: Hirofumi Uto
Reviewer's report:
This study indicated that high-saturate-fat (HFD) diet inhibits diethylnitrosamine
(DEN)-induced hepatocarcinogenesis in Sprague-Dawley rats. In addition, the
inhibition of hepatocarcinogenesis in this study may be due to anti-proliferative
and pro-apoptotic effect of HFD. This study is interesting and may provide novel
mechanism regarding the inhibition of hepatocarcinogenesis by HFD. However,
there were many already-reported facts regarding the effect of high fat diet on
hepatocarcinogenesis, and the analysis of mechanism in this study is not fully
investigated.
Specific comments.
1. The effect of HFD in this study may depend on total calorie intake rather than
fat intake. In fact, HFD restored malnutrition in the DEN-treated rats as stated by
authors. Authors should justify the total calorie intake in the HFD+DEN group and
NCD+DEN group.
2. Rahman et al concluded that the effect of dietary fat during the initiation phase
of AOM-induced hepatocarcinogenesis depends on the type of fat and its fatty
acid composition (Ref 18). Sugie et al also showed that the density and the unit
area of AOM-induced enzyme altered foci in the liver were significantly lower in
the high fish oil group than in the 5% corn oil group and the low fish oil group
(Nutr Cancer. 1995;24:187-95.). In addition, Rahman et al reported that fish oil
rich in polyunsaturated omega-3 fatty acids could inhibit DEN-induced
hepatocarcinogenesis in rats (Jpn J Cancer Res. 1999;90:31-9.). If the effect of
HFD in this study depends on fat rather than total calorie intake, authors should
clarify whether high-saturate-fat or high-unsaturated-fat is better to inhibit
DEN-induced hepatocarcinogenesis.
3. Authors showed the anti-proliferative and pro-apoptotic effect of HFD in rat
liver. Are these effects observed in both tumor cells and non-tumor cells (normal
hepatocytes)?
4. There was an increase in the hepatic level of caspase-3 in the HFD+DEN
group compared to the NCD+DEN group at weeks 10 and 12, and authors
concluded that anti-apoptotic effect may be associated with the attenuation of
hepatocarcinogenesis. However, the hepatic level of caspase-3 in the HFD+DEN
group was significantly lower than that of the NCD+DEN group at weeks 14.
5. Authors stated that there was a more significant reduction in the PCNA
expression in HFD+DEN group at weeks 12 and 14 compared to rats in the
NCD+DEN group (page 7, line 23-). However, the PCNA expression (hepatic
content of PCNA) in HFD+DEN group at weeks 14 was relatively higher than
those in the NCD+DEN group (Fig 2 C).
6. Authors stated that HFD appeared to attenuate the occurrence of HCC and
malignant differentiation in rat HCC model induced by DEN (Page 9, 12-). Three
steps of progression of hepatocarcinogenesis have been proposed: initiation,
promotion, and progression. Authors should discuss this point more in detail.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
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.