A Diet-Induced Obesity (DIO) mouse is a laboratory animal used to understand the impacts of diets high in fat and sugar. Researchers create these models to mirror metabolic changes seen in humans who consume similar diets, which are common in many Western countries. This animal model allows for a controlled investigation into how diet contributes to obesity and related health issues.
The Making of a DIO Mouse
The process of creating a DIO mouse involves placing it on a specialized, high-fat diet. These diets are different from standard rodent food, with some of the most common formulations deriving 60% of their calories from fat. This contrasts with a typical chow diet, which is much lower in fat. The specific diet used can be customized to include high levels of sugar, such as fructose or sucrose, to better replicate human dietary patterns that contribute to metabolic disease.
Not all mice are equally susceptible to gaining weight from this diet. Scientists primarily use specific genetic strains that are predisposed to obesity, with the C57BL/6 mouse being the most widely used due to its reliable response. These mice are started on the high-fat diet at a young age, often around six weeks old.
It takes a considerable amount of time for the mice to develop the full characteristics of obesity. Researchers maintain the mice on this diet for several weeks to months, with some studies extending beyond 18 weeks, to ensure the development of a stable and obese state. During this period, their food intake and body weight are continuously monitored to track the progression toward the desired obese phenotype.
Key Metabolic Consequences
DIO mice undergo significant physiological changes that closely mimic human metabolic syndrome. The most apparent consequence is a substantial increase in body weight and adiposity. The fat accumulation is not just under the skin but also around internal organs, a condition known as ectopic lipid deposition, which is particularly notable in the liver.
Beyond weight gain, the mice develop a condition known as insulin resistance. This means their cells become less responsive to insulin, a hormone that regulates blood sugar. Consequently, the pancreas must produce more insulin to compensate, leading to hyperinsulinemia. Despite this, blood sugar levels often remain high, a state called hyperglycemia, which is a key feature of prediabetes.
These metabolic shifts are accompanied by chronic, low-grade inflammation. The expanded fat tissue releases inflammatory molecules, and there is an observed increase in immune cells like macrophages. Blood tests on these mice also reveal elevated levels of lipids, such as cholesterol and triglycerides, which are additional markers of metabolic dysfunction.
Role in Medical Research
The DIO mouse is a frequently used model in the development of new medicines and treatments for metabolic diseases. It allows researchers to investigate the progression of conditions like obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) in a living system that shares metabolic similarities with humans.
This model is particularly valuable for preclinical testing of new drugs. Before a potential medication can be considered for human trials, it is often first tested in DIO mice to evaluate its effectiveness and safety. For example, researchers can administer a compound and measure its effects on body weight, food intake, blood glucose levels, and insulin sensitivity. This provides data on whether the drug can reverse or slow the diet-induced damage.
Studies using DIO mice have been used for assessing the efficacy of various drug classes, including those targeting weight loss and glycemic control. For instance, the model has been used to demonstrate the effects of GLP-1 receptor agonists like semaglutide, which are now widely used medications for diabetes and obesity. The predictable response of the DIO mouse makes it a tool for bridging the gap between laboratory discovery and clinical application in human health.