Metabolic disease models and translational technologies in non-human primates
Prisys Biotech provides non-human primate (NHP) models and supporting technologies for metabolic disease research and drug development. The portfolio includes Type I diabetes, Type II diabetes, insulin resistance, hyperlipidemia, hypercholesterolemia, obesity, liver steatosis, NASH/MASH, and liver fibrosis. Together, these models address core features of metabolic syndrome and metabolic disease, including dysglycemia, impaired insulin action, abnormal lipid metabolism, excess adiposity, and liver injury.
These models can be combined with glucose and lipid profiling, metabolic challenge tests, imaging, liver biopsy, body-composition analysis, clinical pathology, biosampling, pharmacology, and PK/PD assessments. The model and endpoint package are selected according to the therapeutic mechanism, target biology, modality, and development question.
Metabolic disease models at a glance
Prisys Biotech's NHP metabolic platform covers glucose dysregulation, insulin resistance, abnormal lipid metabolism, obesity, liver steatosis, steatohepatitis, cholestatic liver disease, and liver fibrosis. The following models and study categories are available for protocol discussion, subject to scientific fit, model availability, and study-specific design.
Liver steatosis and NASH/MASH model
The NHP liver steatosis and NASH/MASH model supports research into abnormal hepatic lipid accumulation, steatohepatitis, liver inflammation, hepatocellular injury, and metabolic disease progression. The reference material describes a high trans-fat, high-fructose diet (HFFD) model for hyperlipidemia, MASH, and Type II diabetes-related metabolic phenotypes.
The model can be used to evaluate metabolic therapies, lipid-lowering interventions, insulin-sensitizing approaches, and treatments directed at steatosis or steatohepatitis. The reference material describes different study windows for phenotype development, including a steatosis-dominant phase after approximately four weeks of HFFD and a fibrosis-dominant phase after approximately twelve weeks of HFFD. These time points are reference-study conditions and should not be treated as universal model criteria.
Potential endpoints may include:
- liver fat or steatosis assessment by CT intensity analysis;
- CT-based fat-related measurements, where validated for the study;
- liver biopsy and NAFLD Activity Score (NAS)-related assessment;
- steatosis, lobular inflammation, and hepatocellular ballooning;
- liver enzymes and other clinical chemistry markers;
- glucose, insulin, and lipid profiles; and
- treatment-related changes in hepatic and systemic metabolic biomarkers.
The diet composition, induction duration, baseline liver status, biopsy schedule, imaging method, and endpoint definitions should be established in the protocol.
Liver fibrosis model
The NHP liver fibrosis model supports research into progressive hepatic fibrosis and cholestatic liver disease. The reference material describes a bile duct stenosis (BDS) model in which a defined segment of the distal common bile duct is narrowed and monitored over time.
Potential assessments may include:
- weekly liver-function monitoring;
- ultrasound assessment and evaluation of biliary changes;
- liver biopsy and longitudinal histopathology;
- H&E, Masson's trichrome, and PAS staining;
- collagen deposition and fibrosis scoring;
- biliary sludge or obstruction-related findings; and
- treatment-related changes in liver function and tissue pathology.
The stenosis procedure, monitoring schedule, biopsy time points, control design, and humane endpoints should be confirmed during protocol development. This model should be distinguished from the metabolic HFFD-based NASH/MASH model when defining the primary disease mechanism.
Type II diabetes model
The NHP Type II diabetes model supports the evaluation of therapies for hyperglycemia, impaired glucose regulation, insulin resistance, and related metabolic abnormalities.
The reference material describes an HFFD + STZ model, combining a high trans-fat, high-fructose diet with streptozotocin. This model can be used to study the development of diabetes-related metabolic changes and to evaluate glucose-lowering or insulin-sensitizing therapies.
Potential endpoints may include:
- fasting glucose and serial glucose measurements;
- glucose tolerance or other metabolic challenge tests;
- insulin and related glucose-regulation biomarkers;
- lipid profiles and blood chemistry;
- body weight and body-composition measurements;
- treatment-related changes in glycemic control; and
- PK/PD and biomarker relationships.
The HFFD and STZ exposure schedule, diabetes criteria, treatment window, supportive care, and endpoint panel should be defined in the protocol.
Type I diabetes model
Prisys Biotech supports an exploratory NHP Type I diabetes model for studying insulin deficiency, hyperglycemia, metabolic complications, and treatment response. The reference material describes modeling in juvenile cynomolgus monkeys.
Depending on the study objective, the model may be used to assess insulin replacement, cell or gene therapies, glucose control, and diabetes-associated changes. The reference material notes potential complications such as hyperlipidemia, emaciation, and lens opacity.
Potential endpoints may include:
- fasting and serial blood glucose;
- insulin and other glucose-regulation biomarkers;
- body weight, food intake, and nutritional status;
- lipid profile and blood chemistry;
- ophthalmic or lens-related observations, where relevant;
- organ-function and safety assessments; and
- PK/PD or treatment-response measurements.
The induction approach, disease criteria, age range, duration, monitoring schedule, and humane endpoints require protocol-specific confirmation. Because the reference material labels this model exploratory, its current availability and external positioning should be verified before publication.
Insulin resistance model
The NHP insulin resistance model supports research into impaired insulin action, compensatory hyperinsulinemia, glucose intolerance, and metabolic syndrome-related phenotypes. It can be used to evaluate insulin-sensitizing therapies, incretin-based approaches, metabolic regulators, and other interventions that target glucose homeostasis.
A high trans-fat, high-fructose diet may be used as part of a metabolic induction strategy. The model can be followed longitudinally to assess changes in body weight, glucose regulation, insulin response, lipid metabolism, and treatment effect.
Potential assessments may include:
- fasting glucose and insulin;
- glucose and insulin challenge tests;
- insulin-resistance indices, where defined in the protocol;
- lipid and lipoprotein profiling;
- body weight, food intake, and body composition;
- liver-related metabolic biomarkers; and
- PK/PD and pharmacodynamic biomarkers.
The specific induction method and diagnostic criteria should be selected according to the therapeutic mechanism and the intended clinical development question.
Hyperlipidemia model
The NHP hyperlipidemia model is used to study abnormal lipid metabolism and to evaluate lipid-lowering therapies. The reference material describes a high trans-fat, high-fructose diet (HFFD) designed to induce a controlled metabolic phenotype.
Potential endpoints may include:
- total cholesterol;
- LDL-C and HDL-C;
- triglycerides;
- non-HDL cholesterol or other lipid-related measures;
- glucose and insulin-related biomarkers;
- body weight and body-composition changes; and
- treatment-related changes in lipid and metabolic profiles.
The diet composition, induction duration, baseline criteria, sampling schedule, and lipid panel should be specified before study initiation.
Hypercholesterolemia model
The NHP hypercholesterolemia model supports evaluation of therapies that target elevated cholesterol, lipoprotein metabolism, and related metabolic abnormalities. It may be used to assess small molecules, biologics, nucleic-acid therapies, or other modalities when the target and model are scientifically appropriate.
Potential endpoints include total cholesterol, LDL-C, HDL-C, triglycerides, apolipoproteins, liver-related safety markers, and other protocol-defined lipid or pharmacodynamic biomarkers. Where relevant, imaging may be added to assess vascular or tissue changes associated with abnormal lipid metabolism.
The distinction between hyperlipidemia and hypercholesterolemia should be made in the protocol according to the primary lipid abnormality and the intended treatment effect.
Obesity model
Prisys Biotech supports spontaneous obesity studies in cynomolgus monkeys. The reference material describes obese colonies with high body mass index and uses body-composition imaging to characterize fat, muscle, and bone compartments.
These models can support evaluation of anti-obesity therapies, appetite and food-intake interventions, metabolic regulators, and treatments intended to improve body composition or insulin sensitivity.
Potential endpoints may include:
- body weight and body mass index;
- food intake and intake normalization;
- waist or other protocol-defined anthropometric measurements;
- whole-body DEXA for fat, muscle, and bone composition;
- whole-body CT for fat-volume estimation;
- glucose, insulin, and lipid profiles; and
- treatment-related changes in body composition and metabolic biomarkers.
The reference material includes semaglutide case-study data. Any sponsor-specific drug, dose, sample size, or efficacy result should be removed or separately approved before the content is published as general platform information.
Technologies supporting NHP metabolic disease studies
Prisys Biotech combines NHP metabolic models with metabolic assays, imaging, clinical pathology, biosampling, and pharmacology. A project may use one technology or several methods, depending on the research question.
Glucose and insulin metabolism assays
The platform can support glucose-metabolism studies that characterize glycemic control, insulin response, and treatment-related changes. Depending on the protocol, the assessment package may include:
- fasting and serial glucose measurements;
- insulin measurements;
- glucose tolerance or other metabolic challenge tests;
- insulin-response assessments;
- glucose-regulation biomarkers; and
- PK/PD or pharmacodynamic biomarker analysis.
The final test schedule and calculation method should be defined before study initiation.
Lipid and lipoprotein profiling
Lipid profiling can be used to characterize hyperlipidemia, hypercholesterolemia, obesity-related dyslipidemia, and treatment response. The panel may include total cholesterol, LDL-C, HDL-C, triglycerides, apolipoproteins, and other study-specific lipid measures.
Sampling time points should be aligned with the induction phase, baseline assessment, dosing period, and follow-up requirements.
Body-composition assessment with DEXA and CT
DEXA can provide whole-body estimates of fat, muscle, and bone composition. CT can be used for whole-body fat-volume estimation and, where applicable, tissue-density or organ-related imaging endpoints.
These methods can support obesity, insulin resistance, Type II diabetes, and other metabolic studies in which body composition is part of the therapeutic hypothesis or safety assessment.
Liver imaging and metabolic tissue assessment
For studies that include hepatic metabolic endpoints, imaging and tissue assessment may be combined to follow liver steatosis, NASH/MASH, fibrosis-related changes, cholestatic injury, or treatment response. The reference material describes:
- CT intensity analysis for steatosis-related assessment;
- ultrasound elastography and point shear-wave elastography (pSWE) for tissue stiffness;
- liver biopsy for histopathology and NAS-related assessment;
- H&E, Masson's trichrome, and PAS staining for tissue evaluation; and
- longitudinal evaluation of treatment-related changes.
These methods should be included only when the study question requires liver-related assessment. Any numeric thresholds, case-study results, or claims of model performance should be confirmed against the current validated protocol before publication.
Clinical pathology and biosampling
Blood and other protocol-defined samples can support glucose, insulin, lipid, blood chemistry, liver-function, renal-function, inflammatory, biomarker, PK/PD, and safety analyses. Repeated sampling may be used to follow metabolic induction, treatment response, and recovery when scientifically and ethically appropriate.
The sampling schedule, sample volume, processing method, and analysis plan should be established before study initiation.
Pharmacology and PK/PD
Metabolic models can be integrated with pharmacology and PK/PD assessments to relate dose and exposure to glucose control, insulin sensitivity, lipid lowering, body-weight change, body-composition change, or other metabolic outcomes.
Prisys can support the evaluation of small molecules, biologics, gene therapies, and other modalities when the target, species cross-reactivity, model, and endpoint package are scientifically appropriate.
How the metabolic technologies are combined
A typical metabolic study may connect several evidence streams:
- Metabolic model: establishes diabetes, insulin resistance, dyslipidemia, hypercholesterolemia, obesity-related changes, liver steatosis, NASH/MASH, or liver fibrosis.
- Metabolic assays: measures glucose, insulin, lipids, lipoproteins, and other pharmacodynamic biomarkers.
- Body composition and imaging: characterizes fat, muscle, bone, organ, or liver-related changes.
- Clinical pathology and biosampling: supports safety, mechanism, exposure, and longitudinal response analysis.
- Pharmacology and PK/PD: relates dose and exposure to metabolic and functional outcomes.
- Integrated interpretation: connects the findings to the mechanism of action and the next development decision.
Not every project requires every technology. The appropriate combination depends on the therapeutic modality, target, model, study duration, and decision criteria.
Metabolic disease study planning at Prisys Biotech
Prisys Biotech supports sponsors in defining the NHP model, study endpoints, technology package, and analysis plan before execution. Protocol discussion typically addresses:
- the metabolic mechanism and therapeutic hypothesis;
- the most appropriate model or model combination;
- diet, chemical, spontaneous, or other induction strategy;
- treatment groups, dosing schedule, and study duration;
- primary and secondary glucose, lipid, body-composition, liver, or safety endpoints;
- glucose, insulin, lipid, liver imaging, elastography, biopsy, clinical pathology, PK/PD, or other supporting assessments; and
- data analysis, reporting, and interpretation requirements.
Model availability, induction procedures, diagnostic criteria, disease severity, and endpoint details should be confirmed during protocol development. The final design should reflect the scientific objective and the ethical justification for NHP use.
Selected peer-reviewed studies from Prisys Biotech's metabolic and cardiometabolic programs are listed on our scientific publications page, together with the NHP model and platform capabilities documented in each record.
For related reading, see our articles on NHP preclinical studies in geriatric drug development.
Frequently asked questions
Q: What metabolic disease models does Prisys Biotech offer?
A: Prisys Biotech's NHP metabolic portfolio includes Type I diabetes, Type II diabetes, insulin resistance, hyperlipidemia, hypercholesterolemia, obesity, liver steatosis, NASH/MASH, and liver fibrosis.
Q: What is the HFFD model used for?
A: The high trans-fat, high-fructose diet (HFFD) model can be used to induce or study metabolic phenotypes such as hyperlipidemia, insulin resistance, and Type II diabetes-related changes. The diet composition, duration, diagnostic criteria, and endpoint package should be defined in the study protocol.
Q: How is the NHP Type II diabetes model established?
A: The reference material describes an HFFD + STZ approach that combines a high trans-fat, high-fructose diet with streptozotocin. The final induction schedule, diabetes criteria, treatment window, and monitoring plan require protocol-specific confirmation.
Q: What assessments are used in an obesity study?
A: An NHP obesity study may include body weight, body mass index, food intake, glucose and insulin measurements, lipid profiling, whole-body DEXA, and whole-body CT for body-composition or fat-volume assessment.
Q: Which liver disease models does Prisys Biotech support?
A: Prisys Biotech supports liver steatosis and NASH/MASH research using metabolic induction strategies such as HFFD, as well as liver fibrosis and cholestatic liver disease research using protocol-defined approaches such as bile duct stenosis. Model availability and validation status should be confirmed for each program.
Q: Can metabolic studies include liver imaging or biopsy?
A: Yes. When liver-related metabolic endpoints are relevant, studies may include CT-based steatosis assessment, ultrasound elastography, pSWE, liver biopsy, NAS-related assessment, H&E, Masson's trichrome, PAS staining, histopathology, and liver-related biomarkers. The final package depends on the study question.
Q: What is the difference between the NASH/MASH and liver fibrosis models?
A: The NASH/MASH model is focused on metabolic liver disease with steatosis, inflammation, hepatocellular injury, and possible fibrosis-related progression. The liver fibrosis model described in the reference material uses bile duct stenosis to study progressive fibrosis and cholestatic injury. The two models address different induction mechanisms and should be selected according to the therapeutic hypothesis.
Q: Can metabolic models be combined with PK/PD?
A: Yes. NHP metabolic models can integrate PK/PD, glucose and insulin assays, lipid profiling, body-composition imaging, clinical pathology, biosampling, and other protocol-defined endpoints.
Q: Is the Type I diabetes model established or exploratory?
A: The reference material labels the Type I diabetes model as exploratory. Its current availability, induction method, age range, disease criteria, and external positioning should be confirmed with the Prisys scientific team before publication or study planning.
Discuss your metabolic research program
If you are developing a diabetes, insulin-resistance, lipid-lowering, cholesterol-lowering, obesity, NASH/MASH, liver fibrosis, or other metabolic therapy, contact Prisys Biotech to discuss the appropriate NHP model, technology package, and study endpoints.
