Metabolic diseases including diabetes, obesity and related complications are of high interest in the drug development space largely due to the clinical and commercial success of GLP-1 based therapies.Metabolic disease models are typically classified into induced and engineered models. Induced models include diet-induced obesity and streptozotocin (STZ) to induce type I diabetes while genetically engineered rodent models target specific genes to induce disease phenotype.
There is high interest in developing next-generation weight loss therapies, including sustained release peptide agonists and oral peptide therapies. Therapies that selectively drive fat loss without muscle wasting are also drawing significant clinical attention. Evaluating these therapies in preclinical animal models remains a critical stage of drug development, since in vivo systems capture metabolic and body composition effects that cell-based assays cannot.
Mouse models of obesity and related complications fall into two categories: induced and genetically engineered. Diet is the primary stimulus used to induce an obese phenotype, most commonly through a high fat diet in models such as Diet-Induced Obesity (DIO) mice. Genetically engineered models, such as ApoE variant mice, develop obesity and related lipid abnormalities when exposed to a high fat diet, making them useful for studying both obesity and downstream complications like hyperlipidemia and atherosclerosis.
The Biomere team has experience working with the following models for obesity and related complications:
Disease Indication | Model | Species |
Obesity | Diet-Induced Obesity (DIO) | Mouse |
Ob/Ob Mice | Mouse | |
Hyperlipidemia & Hypercholesteremia | High-Fat, High-Calorie (HFHC) Diet in ApoE Mice | Mouse |
Atherosclerosis |
Large animal models of obesity are more complicated to develop and manage. At Biomere, we have characterized our large animal colony based on body weight, condition, blood chemistry and metabolic profiles. This data allows careful selection of models for each study to reduce data variability.Â
Biomere has metabolic cages available to collect urine and feces for downstream metabolism analysis.Obesity studies typically focus on translational endpoints including body weight, energy expenditure and blood chemistry analysis including glucose, insulin, triglycerides, cholesterol and other metabolic biomarkers. We have deep expertise in evaluating inflammation markers often observed in obesity using ELISA based assays including multiplex MSD panels. In addition to biomarkers, Biomere offers exercise based assays using a treadmill, rotarod and grip strength to evaluate muscle function and therapy induced wasting.
Large animal models of obesity are more complex to develop and manage than rodent models. At Biomere, we characterize our large animal colony based on body weight, body condition, blood chemistry, and metabolic profiles. This characterization allows careful model selection for each study, reducing data variability and strengthening study outcomes.
Biomere offers metabolic cages to collect urine and feces for downstream metabolism analysis. Obesity studies typically focus on translational endpoints, including body weight, energy expenditure, and blood chemistry analysis such as glucose, insulin, triglycerides, cholesterol, and other metabolic biomarkers. The team has deep expertise evaluating inflammation markers commonly observed in obesity using enzyme-linked immunosorbent assay (ELISA) based methods, including multiplex Meso Scale Discovery (MSD) panels. In addition to biomarker analysis, Biomere offers exercise based assays, including treadmill, rotarod, and grip strength testing, to evaluate muscle function and therapy induced wasting.
Figure 1: Changes in body weight and blood glucose in db/db mice treated with either vehicle or the GLP-1 receptor agonist liraglutide (left panels). Changes in body weight and blood glucose in DIO mice fed with either low fat or high fat diet -/+ semaglutide (right panels)Â
Biomere has experience with multiple rodent models of metabolic disease, including obesity, type I and type II diabetes, hyperlipidemia, and hypercholesterolemia. The team has worked with established animal models, including induced and genetically modified models, for type I and type II diabetes. For example, Streptozotocin (STZ) destroys the pancreatic beta cells that produce insulin, mimicking type I diabetes. Type II diabetes models include ob/ob and db/db mice, engineered to be leptin deficient and leptin receptor deficient respectively, and Zucker Diabetic Fatty (ZDF) rats, which carry a leptin receptor mutation (fa/fa) and spontaneously develop insulin resistance, hyperlipidemia, and obesity. Because these rodent models recapitulate many hallmarks of diabetes, they are also used to study related complications such as delayed wound healing and kidney damage. More recently, these models have been used to study the protective effects of glucagon-like peptide-1 (GLP-1) receptor agonist therapies.
Relevant endpoints for metabolic models include body weight, blood glucose, insulin, and hemoglobin A1c (HbA1c) measurements. Additional endpoints include cytokine levels and clinical chemistry markers such as HDL, LDL, total cholesterol, triglycerides, and liver enzymes. Biomere works with specialist partners to offer comprehensive histopathology services, including H&E staining and singleplex and multiplex immunohistochemistry (IHC) and immunofluorescence (IF) analyses.
Biomere has evaluated the following models for diabetes and related complications:
| Disease Indication | Model | Species |
| Type I Diabetes Mellitus | STZ-Induced Diabetes | Mouse, Rat |
| Type II Diabetes Mellitus | OB/OB Mice | Mouse |
| DB/DB Mice | Mouse | |
| Zucker Diabetic Fatty (ZDF) Rat | Rat | |
| Diabetic Nephropathy | STZ Induction +Nephrectomy + High Salt Load | Mouse, Rat |
| Delayed Diabetic Wound Healing | STZ Induction (Type I Diabetes) + Skin Excision | Rat |
| Type II Diabetes (DB/DB Mouse or ZDF Rat) + Skin Excision | Mouse, Rat |
Figure 2: Changes in blood glucose levels of mice treated with Streptozotocin (STZ) over 9 days.
Figure 3: Changes in body weight and blood glucose levels in ZDF rats treated with either vehicle or pioglitazone (an approved therapy to manage type II diabetes).
Biomere uses two categories of mouse models for obesity: induced models, where a high fat diet is the primary stimulus, and genetically engineered models, such as ApoE variant mice. The team also maintains large animal models onsite that have detailed records on body weight and condition and metabolic profiles to support study-specific selection.
Induced obesity models, such as Diet-Induced Obesity (DIO) mice, develop an obese phenotype in response to a high fat diet. Genetically engineered models, such as ob/ob mice, develop obesity and related lipid abnormalities due to lack of leptin that signals satiety. These mice have high food intake resulting in obesity and related complications like hyperlipidemia and atherosclerosis.
A Diet-Induced Obesity (DIO) model is a mouse fed a high fat diet to induce an obese phenotype without genetic modification. DIO mice are widely used to evaluate next-generation weight loss therapies, including sustained release peptide agonists and oral peptide therapies, in a translational in vivo setting.
ApoE variant mice are genetically engineered to develop obesity and lipid abnormalities, including hyperlipidemia and atherosclerosis, when fed a high fat diet. Because the genetic modification predisposes the model to these complications, ApoE mice are useful for studying both obesity and its downstream cardiovascular effects.
While Biomere dose not have a diet induced obese large animal colony, our large animal colony is regularly characterized for body weight and condition and metabolic profiles. This data is useful to identify specific models to evaluate weight loss therapies in a more translationally relevant model.Â
Biomere characterizes its large animal colony in advance, using body weight, body condition, blood chemistry, and metabolic profile data. This lets the team select animals whose baseline characteristics align with a given study’s design and scientific objective.Â
Obesity studies typically include body weight, energy expenditure, and blood chemistry analysis covering glucose, insulin, triglycerides, cholesterol, and other metabolic biomarkers. Biomere also offers metabolic cages for rodent models to collect urine and feces for downstream metabolism analysis.
Yes. Biomere has deep expertise evaluating inflammation markers commonly observed in obesity using enzyme-linked immunosorbent assay (ELISA) based methods, including multiplex Meso Scale Discovery (MSD) panels, which allow simultaneous measurement of multiple inflammatory analytes from a single sample.
Yes. Biomere offers treadmill, rotarod, and grip strength testing to evaluate muscle function and therapy induced wasting. These assays are especially relevant for next-generation weight loss therapies designed to selectively target fat loss without muscle wasting.
Biomere uses Streptozotocin (STZ) induced models for type I diabetes, which destroys the pancreatic beta cells that produce insulin. For type II diabetes, the team uses ob/ob and db/db mice, engineered to be leptin deficient and leptin receptor deficient respectively, along with Zucker Diabetic Fatty (ZDF) rats.
The Zucker Diabetic Fatty (ZDF) rat carries a leptin receptor mutation (fa/fa) and spontaneously develops insulin resistance, hyperlipidemia, and obesity without chemical or surgical induction. This makes it a useful model for studying the interplay between obesity and type II diabetes.
Because ob/ob, db/db, and ZDF models recapitulate many hallmarks of diabetes, they are also used to study related complications such as delayed wound healing and kidney damage. More recently, these models have also been used to study the protective effects of glucagon-like peptide-1 (GLP-1) receptor agonist therapies.
Biomere works with specialist partners to offer H&E staining and singleplex and multiplex immunohistochemistry (IHC) and immunofluorescence (IF) analyses. Clinical chemistry endpoints include HDL, LDL, total cholesterol, triglycerides, liver enzymes, cytokine levels, and hemoglobin A1c (HbA1c).
Biomere offers both rodent and large animal models of obesity and diabetes, characterized colonies for reduced data variability, and a broad endpoint portfolio spanning blood chemistry, inflammation markers, histopathology, and exercise-based functional assays. This breadth supports comprehensive study design execution to thoroughly evaluate novel weight loss and diabetes therapies.
