Positive : Insights

Scientists meticulously design their research studies so they can make conclusive statements about what their results mean. However, firm conclusions from a single study are rarely the final goal. It is usually necessary for outcomes to be replicated by other research groups and labs, long before they can be translated to the clinic. In preclinical research, reproducibility depends on tight control of numerous factors. For example, while the health status of the laboratory animal is critical, there are also environmental factors to consider: diet, bedding, light cycles, noise, humidity… The list goes on. All can have undesired effects on research outcomes.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, with ~24% of the US and European populations estimated to be affected. NAFLD is defined as the presence of fat in liver parenchyma without inflammation, but in the absence of excess alcohol consumption. In many NAFLD cases, a more aggressive form of fatty liver disease develops: Nonalcoholic steatohepatitis (NASH). NASH is associated with liver inflammation, and there is potential for extensive fibrosis to develop, leading eventually to cirrhosis. NAFLD and NASH are therefore increasingly important public health concerns, yet treatment options remain limited.

Although lifestyle management can be effective in bringing NAFLD and NASH under control, it is very difficult to implement and maintain in practice. Therefore, there is an urgent need to develop a deeper understanding of the disease and how it progresses, and to provide additional treatment solutions. Animal models developed through diet manipulation are critically important for achieving these aims. At Envigo, we have a number of diet options available to NAFLD/NASH researchers. Our nutritionists are also available to assist researchers in identifying the diet that best fits their specific research goal.

Many diabetes and obesity research studies rely on diet induced obesity (DIO) models, but there are many options and considerations for maximizing the effectiveness of your study. Two Envigo scientists recently shared their insights on how to select and develop the optimal DIO model that meets your research needs.

A convenient approach to dosing research animals is adding compound(s) to diet. Envigo offers a service that allows researchers to add their compound(s) of interest to animal diets. When adding a compound to a diet, there are some important considerations regarding formulation, compound stability and safety. An Envigo nutritionist can assist you through this process by contacting us at askanutritionist@envigo.com to discuss. Some frequently asked questions about this process are discussed below.

Diet continues to be an overlooked variable in experimental investigations, impacting reproduction, growth, and disease, as well as affecting the response to experimental manipulation in laboratory animals.

Given that reproducibility is a key principle in the conduct and validation of experimental science, how can you ensure that your laboratory animal diet does not unduly influence your outcomes and conclusions drawn from your empirical data?

To answer this question, let’s discuss the function of a diet as a research tool and examine some of the key considerations in choosing the most optimal diet for your study’s needs.

Researchers today have a plethora of options to choose from when it comes to feeding laboratory animals. Let’s explore the differences between standard diets  and custom laboratory animal diets.

Soybean meal, a common ingredient in laboratory animal diets, contains variable levels of phytoestrogens. These plant-derived compounds mimic the structure and function of estrogens in mammals and can have an impact on research results.

The main phytoestrogens (and their primary sources) include:

• isoflavones (mainly genistein and daidzin, which are found in soybean protein),
• coumestans (mainly coumestrol, which is found in alfalfa), and
• ligans (found in flax and sunflower).

Read more about the physiological effects and research variations that can occur, if diets contain isoflavones.

The so-called “silent” liver disease of NASH ranks third for the leading causes of liver transplants and our global obesity epidemic has only increased the prevalence of NASH. Without an approved NASH treatment, the healthcare industry must explore therapeutic strategies for this unmet medical need.

Animal models of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have proven helpful in understanding disease progression, developing new treatment options and improving diagnostic techniques. To produce rodent models of NAFLD and NASH, diet manipulation is a useful tool. When choosing dietary features to induce NAFLD pathologies, researchers should consider the animal model, time frame and desired disease outcome.

Dietary methods to induce NAFLD/NASH in rodents can be split into two categories:

1) Feed rodents for longer periods of time to induce obesity, metabolic syndrome and mild NASH

2) Feed a nutrient deficient diet to induce hepatic features of severe NASH in a relatively short period of time, without inducing metabolic symptoms such as obesity and insulin resistance

Exploring these dietary methods in more detail will help you to make informed decisions about the therapeutic strategies available.

Studying obesity, diabetes, insulin resistance, or other metabolic syndromes requires feeding rodents purified, high-fat diets, but at what age should a high-fat diet be introduced to a model? Which type of high-fat rodent diet can enhance development of obesity phenotypes? To answer these important questions, researchers at Envigo ran a study with 144 male C57BL/6 mice to understand the differences in diet response.

The experiment compared both the age of starting the high-fat diets, as well as the differences between types of high-fat diets. With all models beginning on a fixed formula vegetarian grain-based diet, the experimental groups were formed and given one of three diets: