Targeted Nutrient Modifications in Purified Diets Differentially Affect Nonalcoholic Fatty Liver Disease and Metabolic Disease Development in Rodent Models
Despite a number of researches in the field of NAFLD/ NASH, the specific mechanism to study the development of NAFLD and its progression to NASH is unclear. The number of dietary approaches with specific nutritional components can accelerate the entire spectrum of NAFLD in rodent models and provide a model to acquire further understanding of disease progression in humans. The author Radhakrishnan and colleagues (2020) conducted research titled “Targeted Nutrient Modifications in Purified Diets Differentially Affect Nonalcoholic Fatty Liver Disease and Metabolic Disease Development in Rodent Models” published in The American Society of Nutrition. The summary of the study is given below:
Objective:
To provide a more comprehensive description of dietary strategies in 3 rodent models (mice, rats, and hamsters) to help in the selection of the diet choice during the study design phase.
Method:
The available researches regarding the influence of diet on NAFLD rodent models are reviewed by experts.
Findings:
High-Fat Diets (HFD):
• Dietary modifications commonly used: 30–60 kcal% fat, type of fat plays an important role as higher SFAs increase ER stress, higher ω-6 PUFAs increase oxidative stress, both increase NASH. increase in sucrose or fructose leads to NASH and mild fibrosis.
• Other metabolic effects: increases body weight, body fat, and induce IR/glucose intolerance. In the equal duration of time, HFD incorporation results in only 10% of liver fat concentrations as compare to what accumulates on an MCD diet.
• Matched control diet: Low-fat diet with a matched amount of sucrose or mostly corn starch.
Methionine- and choline-deficient diets (MCD):
• Dietary modifications commonly used: most severe NASH phenotype is produced by MCD diets in the shortest time frame i.e. steatosis (1 wk), NASH/fibrosis in 6–8 wk. Addition of fat (≤60 kcal% fat), fat type typically lard, butter (SFAs), or corn oil (PUFAs), the addition of sucrose and/or cholesterol drives further NASH/fibrosis. Whole protein (such as casein) is replaced with crystalline amino acids with the removal of both methionine and choline, this induces measurable hepatic steatosis, progress to inflammation, and fibrosis.
• Other metabolic effects: Reduces body weight, but 0.1% methionine maintains weight. No IR, reduced plasma lipids. The CD diet-induced rats have IR, weight gain, and higher plasma lipids than the MCD group and those fed a grain-based diet.
• Matched control diet: Methionine- and choline-sufficient diet
Choline-Deficient (CD) high-fat Diets:
• Dietary modifications commonly used: Fat amount (30–60 kcal% fat) Lard commonly used; typically, can drive steatosis, but prolonged feeding (6 mo) can cause fibrosis, impaired glucose tolerance.
• Other metabolic effects: Increases body weight, Less IR than a choline-sufficient diet. On the other hand, The CD diet-fed rats have IR, weight gain, and higher plasma lipids as compare to the MCD group and those fed with a grain-based diet.
• Matched control diet: Low-fat diet with choline.
High-Fructose (HFr) Diet:
• Dietary modifications commonly used: Usually, 60–70 kcal% fructose drives steatosis, NASH. The addition of sucrose (50% fructose) also effective for steatosis, NASH. HFr with 60 kcal% fructose and 10 kcal% fat can lead to higher liver TG, steatosis, and inflammation.
• Other metabolic effects: Increases body weight, IR/glucose intolerance, plasma TGs, blood pressure, markers of oxidative stress and lipogenesis, along with fibrotic markers (typically rats and hamsters)
• Matched control diet: Low-fat diet with 60–70 kcal% as either glucose or corn starch
High-Fat, High-Fructose, High-Cholesterol Combination Diets:
• Dietary modifications commonly used: 40 kcal% fat (trans fat or SFAs), 20–40 kcal% fructose, and 1–2% cholesterol. Fat type and cholesterol increase ER and oxidative stress or fibrosis. Fructose drives steatosis and inflammation.
• Other metabolic effects: Increases body weight, IR/glucose intolerance, Increases plasma lipids.
• Matched control diet: Low-fat diet with 60–70 kcal% as either glucose or corn starch
Dietary NAFLD-Induced HCC:
Some dietary models have shown that the dietary approach for NASH can progress towards HCC when fed for a chronic period. Hence, Unchecked NASH can progress to cirrhosis and may be complicated by hepatocellular carcinoma (HCC).
Control Diets:
The right choice of control diet becomes important in researches using purified diets. Investigators suggest that a defined, purified diet that only differs in the ingredients that are driving NAFLD in the experimental diet should be chosen as the control diet to allow for proper data interpretation.
Image Credit: Food photo created by stockking – www.freepik.com