High-Fat Diet (HFD) induced Obesity Modeling & Pharmacodynamics Service

Creative Biolabs provides a range of well-established, comprehensive high-fat diet-induced obesity models for evaluating the efficacy of weight loss drugs. These models allow for detailed assessment of body weight changes, insulin resistance, glucose metabolism, and lipid profile alterations, helping to facilitate the development of effective therapies for obesity and related metabolic disorders.

Introduction

High-fat diet-induced obesity (HFD-induced obesity) is a widely used animal model for studying human obesity and its associated metabolic disorders. This model is induced by feeding animals a high-fat and high-calorie diet, which leads to excessive accumulation of adipose tissue, insulin resistance, dyslipidemia, and systemic inflammation. The development of obesity in this model closely mimics human metabolic conditions, including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases. Obesity results from an imbalance between energy intake and energy expenditure, where increased caloric intake from fat-rich diets leads to fat accumulation, particularly in the visceral adipose tissue. This adiposity is often accompanied by an increase in inflammatory cytokines and changes in the secretion of adipokines, which impair insulin sensitivity and alter lipid metabolism. Over time, this chronic low-grade inflammation contributes to the development of comorbid conditions such as hypertension, dyslipidemia, and endothelial dysfunction, exacerbating the risk of cardiovascular diseases and diabetes.

Disease Models and Applications

The High-Fat Diet-Induced Obesity (HFDIO) model is commonly used to simulate human obesity and its associated metabolic diseases in rodents and non-rodents (e.g., dogs and NHPs). This model is established by feeding animals a diet that is rich in fats, often supplemented with high-carbohydrate content, leading to significant weight gain and the development of obesity. A key feature of the model is the induction of chronic low-grade inflammation in adipose tissues, contributing to metabolic dysfunction. Advantages of this model include its ability to replicate the hallmark features of obesity in humans, such as insulin resistance and altered lipid profiles, making it a valuable tool for testing anti-obesity drugs and understanding obesity-related diseases. However, a notable limitation is that the model often leads to variability in the extent of obesity and metabolic abnormalities among animals, and it does not fully replicate the complex genetic and environmental factors influencing human obesity. Additionally, long-term use of high-fat diets can lead to liver damage and other organ-related issues, complicating therapeutic assessments.

• Animals: Mouse, Dog, NHPs.
• Simulates: The High-Fat Diet-Induced Obesity (HFDIO) model simulates various human metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), insulin resistance, hyperlipidemia, and cardiovascular disorders. It closely mirrors the pathophysiology of these diseases, such as adiposity, systemic inflammation, dysregulated lipid metabolism, and metabolic dysfunction.
• Evaluates Drugs: This model is used to evaluate drugs targeting obesity and related metabolic conditions. It allows the assessment of anti-obesity agents, insulin sensitizers, glucose-lowering drugs, lipid-lowering therapies, and anti-inflammatory agents. Additionally, it is useful for testing the efficacy of drugs aimed at improving insulin sensitivity, reducing adiposity, and managing comorbidities such as hypertension and dyslipidemia.

Measurements

We offer a variety of measurements for evaluating drug efficacy in High-Fat Diet-Induced Obesity (HFDIO) models, utilizing an array of advanced technologies, including but not limited to:

• General observations: body weight, food and water intake, adiposity index, and clinical signs of obesity-related diseases (e.g., lethargy, skin changes).
• Metabolic analysis: glucose tolerance test (GTT), insulin sensitivity test (ITT), and oral glucose tolerance test (OGTT).
• Lipid profile analysis: serum cholesterol, triglycerides, and low/high-density lipoprotein (LDL/HDL) levels.
• Hematology analysis and serum biomarkers: liver enzymes (ALT, AST), bilirubin levels, and markers of systemic inflammation (e.g., C-reactive protein).
• Histological analysis: adipose tissue morphology, liver tissue (NAFLD scoring), and muscle tissue analysis for fatty infiltration and fibrosis.
• Cytokine profiling (e.g., ELISA): expression of inflammatory mediators such as TNF-α, IL-6, IL-1β, and adipokines (e.g., leptin, adiponectin).
• Gene/protein expression profiling via RT-qPCR and Western blot: investigation of key genes involved in adipogenesis, lipid metabolism, and inflammation (e.g., PPAR-γ, SREBP-1c, FAS).

Related Services

In addition to the High-Fat Diet-Induced Obesity model, other methods can also be used to induce obesity in animal models. These include genetic models, chemical-induced models, and endocrine manipulation approaches.

• High-Fat & High-Carbohydrate Diet induced Obesity Model
• Cafeteria Diet induced Obesity Model
• Monosodium Glutamate (MSG) induced Obesity Model
• ob/ob Obesity Mouse Model

Advantages

• Comprehensive Expertise: We offer extensive experience in developing and evaluating a wide range of animal models for various diseases, including obesity, metabolic disorders, and other complex conditions.
• Advanced Technologies: We utilize cutting-edge technologies and methodologies for accurate, reproducible results, ensuring the highest standards in drug evaluation and research.
• Tailored Solutions: Our team works closely with you to understand your research needs, providing customized models, experimental designs, and data analysis to support your specific objectives.
• Scientific Support: We offer full scientific and technical support at every stage of your project, from initial consultation to data interpretation and reporting.
• Proven Track Record: Our established track record in providing high-quality research services has helped clients across academia, biotechnology, and the pharmaceutical industries successfully advance their projects.
• Flexible Services: Whether you need established models or tailored solutions, we offer flexible services to meet your project's unique requirements, ensuring maximum value and efficiency.

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FAQs

1. Q: What types of animal models do you offer?

   A: We offer a wide range of animal models for various diseases, including obesity, cancer, metabolic disorders, cardiovascular diseases, and liver diseases. We also provide specialized models for preclinical drug evaluation and therapeutic studies.

2. Q: How do you ensure the quality and reliability of your models?

   A: Our models are developed using the latest scientific methods and technologies. We follow strict protocols for model construction, ensuring consistency and reproducibility. Our team conducts regular quality control to meet industry standards.

3. Q: Can you provide customized models for specific research needs?

   A: Yes, we specialize in developing customized animal models based on your specific research requirements. Our scientific team works closely with you to design models that meet your study's objectives.

4. Q: What kind of support do you offer during the project?

   A: We offer full support, including experimental design, model selection, data analysis, and interpretation. Our team of scientists is available throughout the project to assist with any scientific queries or challenges.

5. Q: How long does it take to develop a custom model?

   A: The timeline for developing a custom model depends on the complexity of the disease model and your specific requirements. Generally, it can take anywhere from a few weeks to a few months. We will provide a timeline upon discussing the details of your project.

6. Q: Do you offer data analysis services?

   A: Yes, we offer comprehensive data analysis services, including statistical analysis, gene/protein expression profiling, histological evaluations, and cytokine profiling, among others.

Published Data

Fig. 1 Prolonged HFD-feeding leads to obesity and organ adiposity.¹

This study investigates the onset and progression of inflammatory processes in adipose and hepatic tissues associated with obesity, as well as their role in the development of metabolic inflammation and insulin resistance (IR). To monitor the development of obesity, body weight and adipose tissue (AT) mass were measured in mice fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 24, 40, and 52 weeks, at the ages of 36, 52, and 64 weeks, respectively (Fig. 1A). As anticipated, mice on the HFD exhibited a rapid increase in body weight, which became significant at 12 weeks and continued through the duration of the study (Fig. 1B). From weeks 24 to 40, body weight gradually increased in HFD-fed mice (Fig. 1B; p<0.001) but plateaued between the 40 and 52-week time points. Furthermore, the weights of mesenteric, gonadal/epididymal, and perirenal fat depots were significantly elevated in HFD-fed mice at all time points (24, 40, and 52 weeks) compared to age-matched LFD controls (Fig. 1C-E). No significant differences were observed between these fat depots across the three time points for HFD-fed mice (Fig. 1C-E), indicating a consistent level of adiposity after its initial increase. Additionally, liver weight was notably higher in HFD-fed mice at all durations (24, 40, and 52 weeks) compared to LFD controls (Fig. 1F).

Reference

1. van der Heijden, Roel A et al. "High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice." Aging vol. 7,4 (2015): 256-68. DOI:10.18632/aging.100738. Distributed under an Open Access license CC BY 4.0, without modification.

For Research Use Only.