Diet-Induced Obesity Models and Complication Services

Obesity is a major public health issue in most countries, contributing to the development of diabetes, hypertension, metabolic syndrome, and COVID-19 complications. It also predisposes to the development of various cancers.

We offer well qualified animal models for your metabolic research, providing comprehensive assessment of therapies designed to treat obesity and its comorbidities. Our expert scientists specialize in gold standards of care. We offer the following diet-induced obesity and metabolic syndrome studies:

  • Diet-induced obesity models in C57BL/6 Diet-induced obesity Mice
  • Zucker Fatty Rat Model
  • Diabetic Complication Model

Customizable model development is also available to assess PK/PD relationships and target engagement. All metabolic syndrome studies are supported by biomarker analysis, immunology, pharmacokinetics, and pathology services. In vivo IVIS imaging is available to follow cell and gene therapies.

To further support your cardiovascular and metabolic research, we offer NASH modelsType 1 and Type 2 Diabetes Services, Glucose Tolerance Testing, and Dyslipidemia and Atherosclerosis Models.

 

Diet-Induced Obesity in Mice:

We provide a validated C57BL/6 DIO Mouse model to support your metabolic syndrome studies. The model demonstrates efficacy in animal models with the ability to quantify changes in body composition via qNMR/EchoMRI without sedation or exposure to radiation. Additional assessment of PK/PD relationships and target engagement can be added to further enhance your research.

High Fat Diet Feeding to C57BL/6 Diet-induced obesity Mice:

  • Obesity driven by high fat diet (60% kCal derived from fat)
  • Animals are hyperinsulinemic, insulin resistant, and glucose intolerant
  • C57BL/6 DIO Mouse Model Validation Data:

    Effect of Standards of Care on Body Weight in C57BL/6J DIO Mouse Model

    Line graph showing the Effect of Standards of Care on Body Weight in C57BL/6J DIO mice

    Male DIO mice (18wks of age at study start) were treated with the test articles (PO; QD) for 28 days.

     

    Effect of Standards of Care on Non-Fasting Blood Glucose
    in C57BL/6J Diet-induced obesity Mouse Model

    Line graph showing the effect of Standards of Care on Non-Fasting Blood Glucose in C57BL/6J DIO Mice

    Male DIO mice were treated with the test articles for 28 days to determine the effect of non-fasting blood glucose levels.

     

    Time Post Glucose Challenge in C57BL/6J DIO Mouse Model

    Line graph showing the time Post Glucose Challenge data for the C57BL/6J DIO Mice model

    Blood Glucose levels (mg/dL) were measured in minutes to determine the time post glucose challenge (min).

     

    Effect of Standards of Care on Glycemic Control in C57BL/6J Diet-induced obesity Mouse Model

    Scatter plot showing data for the Effect of Standards of Care on Glycemic Control in C57BL/6J DIO Mice

    Data shows total glucose exposure for different compounds showing the effect of Glycemic Control in C57BL/6J DIO Mice.

     

    C57BL/6J Diet-induced obesity Mice are Hyperinsulinemic

    Scatter plot showing data for serum insulin levels in C57BL/6J DIO Mice

    Graph shows serum insulin levels for lean control mice and C57BL/6J Diet-induced obesity Mice

     

    qNMR Assessment of Body Composition Better Reflects Large
    Differences in Adiposity When Compared to Body Weight

    Bar graph comparing body weight data for both ob/ob and C57BL/6J Mice

    Bar graph comparing the qNMR Assessment of Body Composition for the ob/ob and C57BL/6J mouse model

    The qNMR Assessment of Body Composition shows that the C57BL/6J mouse model has a much lower body fat percentage than the ob/ob mouse model.

     

    Change in Body Weight Composition for the C57BL/6J Diet-induced obesity Mouse Model

    Bar graph data showing the Change in Body weight composition for the C57BL/6J DIO mouse model

     

    Body Composition in DIO Mice after 14 Days on HFD

    Bar Graph showing the body composition percentages in DIO mice after 14 Days on HFD

    Rapid, 14-day protocol to assess effects potential therapeutic agents on body weight loss.

 

Zucker Fatty Rat Services

The Zucker Fatty Rat (ZFR) has been used in metabolic disease research for decades. With related phenotypes of metabolic disease centered around impaired leptin signaling, these strains can be used to provide a rich dataset for investigators looking to assess the efficacy of lead candidate therapies for this multifactorial disease.

The ZFR strain presents as an obese, insulin resistant, glucose intolerant animal model. The strain has been used to investigate various treatment modalities addressing appetite suppression, weight loss, restoration of insulin sensitivity, and reduction of hyperlipidemia. Animals display an elevated serum lipid profile, hyperinsulinemia, and depressed basal and insulin-stimulated glucose transport. Obesity is evident in this strain between 3 – 5 weeks of age and occurs in the face of restricted feeding and is of a hypertrophic/hyperplastic type. The phenotype is driven by defective leptin signaling.

 

Diabetic Complication Models

It is increasingly evident that approval and clinical success of agents treating diabetes can no longer rest on changes in glucose control alone.

What is clear is that the real cost of the disease, both in financial and physiologic terms, comes from complications that attend uncontrolled or poorly controlled glycemia. Virtually all organ systems are impaired in the face of diabetes.

We are keenly aware of this issue, and have continued investigating internally by validating new wound healing models, examining the effects of diabetes on bone health in rodent models, and ensuring that our histological endpoints of the inflammatory side of diabetes are up to speed with the literature. For more information on this topic, please read our blog titled Diabetes Complications: A Long and Lethal List.

 

Talk to an Expert

 

Frequently Asked Questions (FAQs) for Diet-Induced Obesity and Metabolic Syndrome Studies

  • What are the relevant models for studying diet-induced obesity?

    While many species have been used in the study of obesity, the use of rodents predominates in the literature. The application of high fat diets to rats and mice can induce obesity in some strains. Some rat strains are more prone to developing diet-induced obesity (obese prone), while other strains are resistant (obese resistant). By far, the most widely used rodent for studying obesity is the C57BL/6 mouse. The males of this line develop a very robust obese phenotype when fed a high fat diet (60% kCal derived from fat). In our hands, the obese phenotype and the downstream metabolic consequences of obesity are much more pronounced in the C57BL/6 mouse than in rats.

    There are several mutant mouse and rat strains that have also been used in the study of diet-induced obesity. These include the ob/ob and db/db mice, several rat lines including the MCR4 and Zucker fatty rats and some of the associated sub strains.

  • How do I approach the evaluation of therapies designed to induce weight loss?

    Assessing the utility of a therapy targeting weight loss can be quite complicated. It is important to dissect therapeutic efficacy from toxic effects. It is advisable to administer the test article(s) under investigation directly to the animals as opposed to dosing via diet admixture. This obviates effects of decreased food intake due to taste aversion, and it ensures that each animal receives a known amount of test article. Weight loss is usually estimated by recording body weight and food intake, but equally important is the source of the weight loss. This is addressed through body composition measurements. We perform this using EchoMRI, which can be performed quickly on conscious animals and does not require the use of radiation. Finally, clinical chemistry and some immunologic parameters can be helpful to differentiate between loss of adipose tissue and muscle wasting.

  • What are some important endpoints that I might include in my metabolic syndrome study?

    In addition to the physical and immunologic parameters mentioned above, quantifying measurements of insulin sensitivity, glycemic control, hepatic glucose output, and dyslipidemia would demonstrate an overall improvement in whole body physiology.