Metabolic Assessment Techniques in Mouse Models

Mouse models are indispensable for investigating the mechanisms underlying energy balance, glucose homeostasis and lipid metabolism. A diverse array of techniques has been developed to characterise metabolic phenotypes in vivo. Glucose tolerance tests and insulin tolerance tests probe whole-body glycaemic control, while the hyperinsulinaemic-euglycaemic clamp remains the gold standard for quantifying insulin sensitivity. Indirect calorimetry systems measure oxygen consumption and carbon dioxide production to infer energy expenditure and substrate utilisation. Stable-isotope tracers enable partitioning of endogenous versus exogenous substrate fluxes, revealing rates of gluconeogenesis, lipogenesis and fatty-acid oxidation. Body composition can be assessed non-invasively by densitometry or dual-energy X-ray absorptiometry, and magnetic resonance imaging provides serial measurements of adipose and lean mass. Telemetry and continuous glucose monitoring facilitate high-resolution tracking of physiological parameters without repeated handling. Together, these approaches allow integrated characterisation of diet-induced obesity, genetic manipulations and pharmacological interventions, accelerating translation from bench to bedside.

Research from Nature Portfolio

Recent investigations employing genetic and metabolomic strategies have refined our understanding of lipid-sensing pathways and pathway flux during dietary interventions. One study demonstrated that deletion of the protein kinase R gene does not alter weight gain, hepatic steatosis or systemic glucose tolerance in mice fed a high-fat diet, thereby challenging the proposed role of this kinase in driving inflammation and obesity-associated complications. Another report combined stable isotope labelling with targeted lipidomics to dissect the early hepatic response to switching from a high-fat, high-sucrose regimen back to standard chow. This work revealed a rapid suppression of de novo lipogenesis and partial normalisation of glycerolipid synthesis despite residual lipid stores, highlighting dynamic shifts in hepatic metabolic flux during weight loss.

Metabolic Assessment Techniques in Mouse Models publication trend

The graph below shows the total number of articles in metabolic assessment techniques in mouse models across all publications each year (not limited to Nature Index journals).

Technical terms

Glucose tolerance test (GTT): An assay in which glucose is administered and blood glucose is measured over time to assess whole-body glucose disposal.

Hyperinsulinaemic-euglycaemic clamp: A procedure in which insulin is infused at a fixed rate while glucose is clamped to a target concentration, quantifying insulin-stimulated glucose uptake.

Indirect calorimetry: Measurement of O₂ consumption and CO₂ production to infer energy expenditure and substrate oxidation rates.

Stable-isotope tracer: A non-radioactive isotope used to trace metabolic pathways and quantify substrate fluxes in vivo.

Dual-energy X-ray absorptiometry (DEXA): A non-invasive imaging technique for quantifying bone mineral density, lean mass and fat mass.

References

1. Methods and Models for Metabolic Assessment in Mice. Journal of Diabetes Research (2013).
2. PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications. Nature Communications (2016).
3. Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis. Scientific Reports (2016).
4. Comparative analysis of oral and intraperitoneal glucose tolerance tests in mice. Molecular Metabolism (2022).
5. Translating glucose tolerance data from mice to humans: Insights from stable isotope labelled glucose tolerance tests. Molecular Metabolism (2021).
6. The use of mice in diabetes research: The impact of physiological characteristics, choice of model and husbandry practices. Diabetic Medicine (2021).