The Diet-Induced Obesity (DIO) Mouse Model

Q: How long is the high-fat diet induction of the DIO mouse model, and what body weight or metabolic endpoint defines established obesity?

The high-fat diet (HFD) induction period typically ranges from 8 to 16 weeks, depending on the desired severity and strain. We aim for a statistically significant difference in body weight (e.g., 15-20% difference from lean controls) and an established state of insulin resistance, before commencing the therapeutic intervention phase.

Q: Besides body weight, what key metabolic parameters are routinely measured, and what diet-matched control group is used?

Key metabolic parameters routinely measured include Fasting Blood Glucose, a full Glucose Tolerance Test (GTT) or Insulin Tolerance Test (ITT), and a terminal Lipid Profile (e.g., triglycerides, total cholesterol). The essential control group is the Diet-Matched Lean Control (e.g., animals on a low-fat diet, which is also used as the vehicle control for all dosing). Secondary measurements often include food intake and body composition (e.g., DEXA scan).

Explore obesity’s impact on metabolic, cardiovascular, and inflammatory diseases.

The DIO mouse model offers a translational platform to study the physiological and metabolic changes seen in human obesity. Ideal for researchers evaluating novel therapeutics targeting weight loss, glucose metabolism, inflammation, and other obesity-driven complications, the DIO mouse model reliably gains weight, develops insulin resistance, and exhibits other hallmarks of obesity-related diseases.

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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

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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.

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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.

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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.

Publications

Chu, D. T., Malinowska, E., Jura, M., & Kozak, L. P. (2017). C57 BL/6J mice as a polygenic developmental model of diet‐induced obesity. Physiological reports, 5(7), e13093. 10.14814/phy2.13093

Li, J., Wu, H., Liu, Y., & Yang, L. (2020). High fat diet induced obesity model using four strains of mice: Kunming, C57BL/6, BALB/c and ICR. Experimental animals, 69(3), 326-335. 10.1538/expanim.19-0148

Nunn, E., Jaiswal, N., Gavin, M., Uehara, K., Stefkovich, M., Drareni, K., … & Titchenell, P. M. (2024). Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism. Molecular Metabolism, 80, 101880. 10.1016/j.molmet.2024.101880

Xiang, J., Qin, L., Zhong, J., Xia, N., & Liang, Y. (2023). GLP-1RA liraglutide and semaglutide improves obesity-induced muscle atrophy via SIRT1 pathway. Diabetes, Metabolic Syndrome and Obesity, 2433-2446. 10.2147/DMSO.S425642

Frequently Asked Questions

How long is the high-fat diet induction of the DIO mouse model, and what body weight or metabolic endpoint defines established obesity?

The high-fat diet (HFD) induction period typically ranges from 8 to 16 weeks, depending on the desired severity and strain. We aim for a statistically significant difference in body weight (e.g., 15-20% difference from lean controls) and an established state of insulin resistance, before commencing the therapeutic intervention phase.

Besides body weight, what key metabolic parameters are routinely measured, and what diet-matched control group is used?

Key metabolic parameters routinely measured include Fasting Blood Glucose, a full Glucose Tolerance Test (GTT) or Insulin Tolerance Test (ITT), and a terminal Lipid Profile (e.g., triglycerides, total cholesterol). The essential control group is the Diet-Matched Lean Control (e.g., animals on a low-fat diet, which is also used as the vehicle control for all dosing). Secondary measurements often include food intake and body composition (e.g., DEXA scan).

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

The Diet-Induced Obesity (DIO) Mouse Model

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A Model that Mirrors the Real-World Progression of Obesity