The focus of IPST’s cardiometabolic lab, under the direction of Senior Research Scientist Dr. Sébastien Labbé, is to inform pre-clinical drug development in diabetes, obesity and metabolic disease.

  • Worldwide obesity has nearly tripled since 1975.
  • In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese.
  • 39% of adults aged 18 years and over were overweight in 2016, and 13% were obese.
  • Most of the world’s population live in countries where overweight and obesity kills more people than underweight.
  • 41 million children under the age of 5 were overweight or obese in 2016.
  • Over 340 million children and adolescents aged 5-19 were overweight or obese in 2016.

The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended.

Raised Body Mass Index (BMI) is a major risk factor for noncommunicable diseases such as:

  • cardiovascular diseases (mainly heart disease and stroke), which were the leading cause of death in 2012;
  • diabetes;
  • musculoskeletal disorders (especially osteoarthritis – a highly disabling degenerative disease of the joints);
  • some cancers (including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon).

The risk for these noncommunicable diseases increases, with increases in BMI.

Childhood obesity is associated with a higher chance of obesity, premature death and disability in adulthood. But in addition to increased future risks, obese children experience breathing difficulties, increased risk of fractures, hypertension, early markers of cardiovascular disease, insulin resistance and psychological effects.

Liver fibrosis represents a classical outcome of many chronic liver diseases irrespectively of the etiology of injury. It results from successive rounds of chronic activation of the physiological wound-healing response that sustains persistent fibrogenesis and leads to progressive fibrosis of the organ through inflammation or reactive oxygen species mechanism.

CCl 4-induced liver fibrosis

HFHF-induced liver fibrosis

MCDD-induced liver fibrosis

Plasma Protein Binding Assay

The study is best suited to quantify the bioavailability of test article. Determine the free vs. bound ratio of test article in human blood using an equilibrium dialysis assay.

Metabolic profiles

  • Cell-based assays are a powerful tool for drug efficacy discovery. IPST‘s cardiometabolic lab offers some interesting endpoints including substrates metabolism (glucose and lipid uptake) in adipose, muscular, hepatocyte and cardiomyocyte cells.
    • Respiratory capacity (a surrogate for energetic status)
      • cell oxygen consumption
      • cell C02 production
      • cell respiratory exchange ratio
  • In vivo-based assays provide powerful efficacy models to evaluate test articles on different metabolic diseases – with a focus on exercise activity, metabolic disorders associated with obesity, and type 2 diabetes, i.e., dyslipidemia, atherosclerosis, hepatic steatosis, adipose tissue remodelling, cardiomyopathy and insulin resistance.
    • Exercise
    • Obesity
    • Diabetes
  • In vivo heart rate and body temperature recording. Metabolic abnormalities have been linked to hormonal and substrates changes in the blood. Such modifications have a direct impact on cardiac functionalities. IPST‘s cardiometabolic lab offers heart rate monitoring over prolonged periods of time to evaluate the effect of test articles on cardiac function.

Metabolic screening

Cardiovascular complications are the leading cause of diabetes-related morbidity and mortality. Type 2 diabetes cardiomyopathy is one of the major cardiovascular complications independent of coronary artery disease and hypertension. This has led to a ventricular dysfunction with diastolic and systolic issues. The prevalence of which may be as high as 60% even in well-controlled type 2 diabetes patients.

Type 2 Diabetes Cardiomyopathy

Measurements available:

    • food intake and food choice
    • energy expenditure and RQ
    • thermic response to food
    • basal metabolic rate at thermoneutrality
    • metabolic parameters such as glucose, lactate, lipids
    • hormones such as insulin, glucagon, active and total GLP-1, and adipokines
    • glucose tolerance, insulin tolerance and pyruvate tolerance
    • euglycemic hyperinsulinemic clamps
    • hepatic glucose output and tissue glucose uptake rates
    • isolated hepatocytes and adipocytes
    • isolated muscle
    • microarrays, RNA analysis and Western blots
    • liver and muscle toxicology markers
    • real time inflammatory markers
    • bioinformatics; automated imaging tools
    • cell culture
    • central administration
    • immunohistochemistry