Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet

Chen, Yung Ju; Wallig, Matthew A.; Jeffery, Elizabeth H.

doi:10.3945/jn.115.228148

Cited by 53 publications

(50 citation statements)

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“…However, a diet high in fat (e.g., lard from bacon consumption) has long been considered as a risk factor for IBD and colon cancer [29,30]. Therefore, although lard contains certain amount of linoleic acid, the diet in this study is a widely accepted high (lard) fat diet for animal models to address diet-induced obesity issue which is partially related to a Western diet [31,32].…”

Section: Discussionmentioning

confidence: 99%

Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice

Zeng

Ishaq

Zhao

et al. 2016

The Journal of Nutritional Biochemistry

153

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Consumption of an obesigenic/high-fat diet (HFD) is associated with a high colon cancer risk and may alter the gut microbiota. To test the hypothesis that long-term high-fat (HF) feeding accelerates inflammatory process and changes gut microbiome composition, C57BL/6 mice were fed HFD (45% energy) or a low-fat (LF) diet (10% energy) for 36 weeks. At the end of the study, body weights in the HF group were 35% greater than those in the LF group. These changes were associated with dramatic increases in body fat composition, inflammatory cell infiltration, inducible nitric oxide synthase protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, β-catenin expression was increased in colon (but not ileum). Consistent with gut inflammation phenotype, we also found that plasma leptin, interleukin 6 and tumor necrosis factor α concentrations were also elevated in mice fed the HFD, indicative of chronic inflammation. Fecal DNA was extracted and the V1-V3 hypervariable region of the microbial 16S rRNA gene was amplified using primers suitable for 454 pyrosequencing. Compared to the LF group, the HF group had high proportions of bacteria from the family Lachnospiraceae/Streptococcaceae, which is known to be involved in the development of metabolic disorders, diabetes and colon cancer. Taken together, our data demonstrate, for the first time, that long-term HF consumption not only increases inflammatory status but also accompanies an increase of colonic β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of C57BL/6 mice.

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Section: Discussionmentioning

confidence: 99%

Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice

Zeng

Ishaq

Zhao

et al. 2016

The Journal of Nutritional Biochemistry

153

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“…Studies show that broccoli protects against the development of NAFLD and liver adenomas in mice fed an HF diet and treated with diethylnitrosamine (an agent that induces hepatocellular carcinoma in mice). Mice fed an HF diet (19% fat and 31% sucrose) and 10% broccoli had decreased liver weight, hepatic TGs, plasma ALT concentrations, and number of liver nodules and adenomas compared with mice fed an HF diet without broccoli (93). In this study, mice were started on a Western diet and 10% broccoli at 5 wk before induction with diethylnitrosamine at 6 wk (93).…”

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confidence: 99%

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease

Hsu

Ness

Kowdley

2017

Advances in Nutrition

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Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of $5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. Adv Nutr 2017;8:253-65.

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“…However, the development of nasal cavity neoplasm has not been reported for any route of DEN administration in the mouse model. As part of a larger study of the impact of DEN and a Western (high fat/ high sugar) diet on liver health (Chen et al , 2016), we observed difficulty in breathing in many DEN-treated animals, independent of dietary treatment. Here we report the appearance of multiple nasal epithelial neoplastic lesions, visible externally in only one instance, induced by intraperitoneal treatment with DEN.…”

Section: Introductionmentioning

confidence: 87%

“…Experimental design and diet formulae are described in a previous report (Chen et al , 2016) and summarized below. Seventy-two male 4-week-old B6C3F1 (male C3H/HeJ × female C57Bl/6J) mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The original objective was to evaluate the impact of a Western diet with or without 10% broccoli on DEN-induced on liver cancer. We administered DEN (45 mg/kg) ip to young adult male B6C3F1 mice by six weekly injections, and evaluated liver cancer six months after the DEN treatments (Chen et al , 2016). Here we report unexpected primary tumorigenesis in nasal epithelium, independent of dietary treatment.…”

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confidence: 99%

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Nasal Tumorigenesis in B6C3F1 Mice Following Intraperitoneal Diethylnitrosamine

2016

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Diethylnitrosamine (DEN) is a chemical broadly used in animal models as a hepato-carcinogen, reported to also cause pulmonary neoplasms in mice. The original objective was to evaluate the impact of a Western diet with or without 10% broccoli on DEN-induced on liver cancer. We administered DEN (45 mg/kg) ip to young adult male B6C3F1 mice by six weekly injections, and evaluated liver cancer six months after the DEN treatments (Chen et al., 2016). Here we report unexpected primary tumorigenesis in nasal epithelium, independent of dietary treatment. More than 50% of DEN-treated B6C3F1 mice developed nasal neoplasm-related lesions, not reported previously in the literature. Only one of these neoplasms was visible externally prior to post mortem examination. Intraperitoneal DEN treatment used as a model for liver cancer can have a carcinogenic effect on the nasal epithelium in B6C3F1 mice, which should be carefully monitored in future liver cancer studies.

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Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet

Abstract: Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice.

Cited by 53 publications

References 64 publications

Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice

Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease

Nasal Tumorigenesis in B6C3F1 Mice Following Intraperitoneal Diethylnitrosamine

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