Metabolic Phenotyping Core Facility
An Institutional Shared Resource
Based in the Department of Medicine
At Rutgers-Robert Wood Johnson Medical School
Table of Contents
Overview
The Metabolic Phenotyping Core Facility provides investigators with services to comprehensively assess metabolism in rodents. This is particularly relevant if one is interested in understanding the role of genes or drugs in controlling metabolism, and given the huge cost of the obesity and diabetes epidemic this has potential relevance to many investigators at Rutgers that do not work on metabolism, but may have stumbled upon a metabolic phenotype that may potentially have relevance for obesity and diabetes.
We provide advice on experimental design and metabolic phenotyping capabilities such as Indirect calorimetry, body composition, metabolic turnover studies and hyperinsulinemic euglycemic clamp analysis in live animals, that includes data analysis and interpretation. Do not hesitate to contact us if you are considering using our services.
Services
Indirect Calorimetry
To assess energy homeostasis including oxygen consumption, CO2 production, respiratory exchange ratio through indirect calorimetry, and in addition food intake and activity monitoring.
The core can perform indirect calorimetry for up to 24 animals in parallel (8 Comprehensive Laboratory Animal Monitoring System (CLAMS, Columbus Instrument) and 16 TSE metabolic cages). Eight of these indirect calorimetric cages are placed in one environmental chamber that allows the manipulation of the ambient temperature where the animals can be housed at a set temperature in a range from 4°C to 30°C to assess how metabolism is regulated during cold exposure or thermoneutrality commonly believed to be around 28°C. The latter is important as many metabolic functions are influenced by the ambient temperature and the argument has been made that mice are under constant moderate cold stress at room temperature which changes the susceptibility to fatty liver and metabolic disease. Hence, conventionally housed mice are not a good model for human disease since humans wear clothes and do not experience cold stress. Thus, it is informative to study mice at thermoneutrality as a more suitable model for human conditions, which the environmental chamber allows to do. The profound impact of ambient temperature on experimental outcome is now appreciated not only in the metabolism, but also for example in the immunology field.
Body Composition
The ratio of lean mass and fat mass is critical to study/understand energy homeostasis and metabolic disease. The EchoMRI measures lean mass, fat mass and free water content in restrained conscious mice using MRI. Body composition is assessed without anesthesia in less than three minutes, this can be repeated to confirm reproducibility as well as serially to monitor the effect of an obesity or drug treatment and/or specific gene ablation in metabolic control.
Tracer Infusion Studies
To determine metabolic flux and the turnover rate of specific molecules and contribution of labeled substrates to metabolism and metabolic control, the core provides metabolomics analysis using stable-isotope labeled tracer infusion and LC/MS. Tracers are infused through the right jugular vein to establish and maintain a steady state for 6h, and serum samples are collected and derivatized to analyze with LC/MS (LC/MS is conducted by Metabolomics Core). Enrichment of metabolites and flux analysis are conducted to determine the distribution of specific carbon source and turnover rate of metabolites. These results provide fundamental metabolic information in diabetes, NAFLD, cardiovascular disease and cancer. Metabolomics analysis is a critical technique to overcome the limitation of traditional metabolomics studies such as bolus injection because infusion maintains steady state of metabolism, and state of the art LC/MS system enables to determine the enrichment and flux rate of many metabolites in the same sample.
Hyperinsulinemic-Euglycemic Clamp
To study glucose metabolism and insulin action in mice, the core provides hyperinsulinemic euglycemic clamp using stable-isotope labeled 6,6-D2 glucose infusion and LC/MS. 6,6-D2 glucose is infused through right jugular vein for 3h for basal clamp and then 6,6-D2 glucose plus insulin and 50% (w/v) glucose are infused for 3h to maintain euglycemia. Serum is collected to determine glucose enrichment and turnover rate using LC/MS. This result provides key parameters of insulin action such as the glucose infusion rate and the rate of hepatic glucose production in the basal state and the hyperinsulinemic clamp period. Hyperinsulinemic euglycemic clamp in this core uses stable-isotope labeled tracer instead of traditional radioisotope and LC/MS, providing more accurate results and a safer methodology as no radioactivity is involved.
Resource Team
Scientific Director:
Christoph Buettner, M.D., Ph.D.
Professor and Division Chief
Division of Endocrinology, Metabolism and Nutrition
Department of Medicine
Rutgers-Robert Wood Johnson Medical School
Executive Director:
Hyok Joon Kwon, Ph.D.
Assistant Professor
Division of Endocrinology, Metabolism and Nutrition
Department of Medicine
Rutgers-Robert Wood Johnson Medical School
Email: hyokjoon.kwon@rutgers.edu
Equipment
Metabolic Phenotyping Core Facility is located on the basement of animal facility at Child Health Institute of New Jersey. Instrumentation includes:
- Eight cages of Comprehensive Laboratory Animal Monitoring System (CLAMS, Columbus Instrument) for indirect calorimetry
- Sixteen TSE metabolic cages with environmental chambers for indirect calorimetry.
- EchoMRI-100 Whole-body body composition analyzer
- Infusion pumps and swivel and tether systems for stable isotope tracer infusion
- Anatomical Microscope and surgery station
Pricing
The Metabolic Phenotyping Core Facility provides services such as indirect calorimetry, body composition and hyperinsulinemic euglycemic clamp at the cost listed below.
Items | Price ($/mouse) Inside | Price ($/mouse) Outside | |
Body composition | 10 | 20 | |
Tolerance test (Glucose, insulin, pyruvate and glycerol) | 40 | 80 | |
Jugular vein catheter implantation surgery | 100 | 200 | |
Arterial catheter implantation surgery | 100 | 200 | |
Jugular vein and arterial catheter implantation surgery | 150 | 300 | |
Indirect calorimetry | 120 | 240 | |
Indirect calorimetry with environmental chamber | 150 | 300 | |
Indirect calorimetry analysis | 30 | 60 | |
Euglycemic clamp | 200 | 400 | |
Euglycemic clamp analysis (LC/MS and data analysis) | 30 | 60 | |
Infusion of stable-isotope tracers and serum preparation for metabolomics | 100 | 200 | |
Metabolomics analysis (sample derivatization, LC/MS and data analysis) | 30 | 60 | |
1. LC/MS and MS data analysis are conducted in Metabolomics Core (New Brunswick, Xiaoyang Su, Ph.D.)
2. Stable-isotope tracers such as 13C6-Glucose, 2D-Glucose, 13C3-pyruvate, 13C3-lactate and 13C3-glycerol for metabolomics study is provided by investigators.
Service Request Form
Contact Us
To schedule an appointment, discuss experiments or request pricing:
Executive Director:
Hyok Joon Kwon, Ph.D.
Assistant Professor
Division of Endocrinology, Metabolism and Nutrition
Department of Medicine
Rutgers-Robert Wood Johnson Medical School
Email: hyokjoon.kwon@rutgers.edu
Phone: 732-235-4909
Locations:
Office:
Clinical Academic Building
125 Paterson Street, Room 7150
New Brunswick, NJ 08901
Animal Facility:
89 French Street, Basement Room 204
New Brunswick, NJ 08901