The Diet-Induced Obesity (DIO) Mouse Model

A Model that Mirrors the Real-World Progression of Obesity

Unlike genetic obesity models, the DIO mouse model provides a nutritionally induced approach, making it an effective tool for studying environmental and lifestyle-driven obesity. The controlled high-fat diet protocol allows you to simulate real-world metabolic changes, including shifts in adiposity, glucose regulation, and lipid metabolism. Because obesity develops over time, this model captures both early metabolic adaptations and long-term disease progression, providing a more physiologically relevant platform for therapeutic evaluation.

With over two decades of experience, Melior has been at the forefront of metabolic disease research, collaborating with leading pharmaceutical companies and academic institutions to refine preclinical models. This expertise ensures that your DIO studies are rigorously designed, generating highly translatable insights for obesity-driven conditions such as type 2 diabetes, cardiovascular disease, and inflammatory disorders.

Advantages of the Diet-Induced Obesity Model

  • Track adiposity and muscle mass over time with dual-energy x-ray absorptiometry (DEXA) imaging
  • Reproducibly develop metabolic dysfunction under high-fat diet conditions
  • Generate more physiologically relevant data than genetic models for obesity
  • Capture early metabolic changes and long-term disease progression

This model is included in our theraTRACE® platform

We can customize your obesity study

Tailor your study with bespoke protocols, including DEXA imaging for body composition analysis, food intake monitoring, blood chemistry, glucose tolerance tests, and insulin sensitivity assessments.

Expand disease indications in the context of diet-induced obesity, including aging, inflammation, and psychiatric endpoints such as depression.

Interested in running an Insulin Tolerance Test study?

The Insulin Tolerance Test (ITT) is a key tool for measuring insulin sensitivity and glucose metabolism in preclinical models. This test provides critical insights into metabolic dysfunction and the efficacy of anti-diabetic therapies.

  • We chose Melior Discovery because they were responsive and cost effective.  We are staying with them as a chosen scientific partner because of their thoughtful scientific input to experimental design and attention to detail.  Their expertise and flexibility allowed us to quickly adapt the study design and evaluate additional outcome measures to pursue unexpected activity.

    Sridharan Rajamani, Ph.D., Senior Research Scientist

    Gilead Sciences
  • I have been working with Melior on a number of projects over the course of a few years now.  They have been a great partner throughout this time.  The scientists whom I have worked with have been great problem-solvers and were customer focused.

    Jay Lichter

    Avalon Ventures
  • Melior provided State-of-the-art Preclinical Pharmacology Support for a period of nearly a year where a series of in vivo studies were completed on a weekly basis. The staff was extremely user-friendly and the operational processes were excellent. I can recommend Melior without reservation.

    Richard DiMarchi, PhD

    Cox Professor of Chemistry & Gill Chair in Biomolecular Sciences Indiana University, Department of Chemistry
  • Because Melior could do the orthotopic intracranial implants, we were able to do survival studies with brain tumor-bearing animals that were treated with our therapy, showing a beautiful survival with our agent versus control. Talk about something that gets your investors going! These beautiful survival curves with our agent versus control and visual photos are in all of our investor decks because… it's powerful.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Melior works in many therapeutic areas, like CNS, inflammatory disease, GI, cardiovascular, and oncology. I was very pleased that when it came to doing tumor studies, both subcutaneous and intracranial, they did them well. They reported on the studies on time and did the data analysis really well.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Their areas of expertise are extensive, and they are very experienced, responsive, and flexible in terms of how the study is run. Their pricing is reasonable, making them the best option for a young, not well-funded company like ours.

    Maxine Gowen

    Tamuro Bio
  • Melior’s team was very experienced and knowledgeable. They were always very open to suggestions and questions, spending a lot of time helping us feel comfortable with the study design. I would give them very high marks.

    Maxine Gowen

    Tamuro Bio
  • The most important factors in choosing to work with Melior were the fit between the tests they could run and our needs, as well as their tight budget and proximity. Melior was the best fit for our research goals.

    Ira Spector

    SFA Therapeutics

Fat and Lean Mass and percentage changes. DEXA analysis was performed at Baseline and on Weeks 2 and 4. All mice shared comparable fat/lean mass and fat percentage at the baseline. Compared to the mice of the DIO+Vehicle group, the mice of the DIO+SEMA group showed significantly reduced fat mass and fat percentage at weeks 2 and 4. Values show mean ±SEM (n=11 for DIO+SEMA, N=5 for DIO+Vehicle). Data were analyzed by 1-way ANOVA with Dunnett’s MCT with comparison to the DIO+Vehicle group. *P<0.05, **P<0.01, *** P<0.001, ****P<0.0001.

Body weights and food intake. Animals were weighed, and food intake was captured twice per week for the duration of the study. Compared to the DIO+Vehicle group, the mice of the DIO+SEMA group showed significant bodyweight reductions from Day 8 until the end of the study and reduced food consumption from day 8 until day 25. Values show mean ±SEM (n=11for DIO+SEMA, n=5 for DIO+Vehicle). Data were analyzed by 2-way ANOVA with Dunnett’s MCT.

Fasting Blood Glucose. Fasting glucose was measured at Baseline and on Week 4. The SEMA-treated group exhibited significantly reduced fasting glucose levels after 4 weeks of treatment compared to the DIO+Vehicle group. Values show mean ±SEM (n=11 for DIO+SEMA, N=5 for DIO+Vehicle). Data were analyzed by 1-way ANOVA with Dunnett’s MCT. *P<0.05.

Frequently Asked Questions

How long does it take to establish the DIO mouse model?

To induce obesity, mice are typically placed on a high-fat diet for 10–16 weeks beginning at 6 weeks of age.

Studies evaluating GLP-1 analogs or other interventions can range from 2–6 weeks, but based on research needs, durations from 1 day to several months are possible.

What metabolic assessments can be performed using this model?

This DIO model supports a range of metabolic assessments to evaluate glucose metabolism, insulin function, and energy balance, including:

  • DEXA imaging for body composition analysis (adiposity and muscle mass)
  • Food intake monitoring
  • Fasting glucose measurements for baseline metabolic status
  • Insulin Tolerance Test (ITT)
  • Oral Glucose Tolerance Test (GTT)
  • Hyperinsulinemic-euglycemic clamp for precise insulin function analysis
  • Blood chemistry analysis for glucose and lipid metabolism markers

As well as non-metabolic assessments, including:

  • Histology
  • Inflammatory markers
  • Psychiatric endpoints (e.g., depression-related behavioral tests)
Can this DIO model be used to study diseases beyond metabolic disorders?

Yes! While commonly used for obesity, diabetes, and metabolic syndrome, our DIO mouse model can also support research into aging, inflammation, and psychiatric conditions such as depression, providing a broader view of obesity’s systemic effects.

Citations

Lang, P., Hasselwander, S., Li, H., & Xia, N. (2019). Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice. Scientific reports, 9(1), 19556. https://doi.org/10.1038/s41598-019-55987-x

Li, Y., Li, X., Xue, Q., Wang, J., & Tan, J. (2021). High-fat diet and dyslipidemia synergistically contribute to T cell senescence in gut associated lymphoid tissue. Experimental gerontology, 151, 111404. https://doi.org/10.1016/j.exger.2021.111404