Improving reproducibility of metabolic research

Reactive oxygen species (ROS) have important roles in health and disease, but are chemically complex and difficult to measure accurately. This consensus statement proposes guidelines and best practices on the nomenclature and assessment of ROS, oxidative reactions and oxidative damage in cells, tissues and in vivo.

In this Perspective, the authors discuss the various mouse preclinical models that are available for the study of non-alcoholic steatohepatitis (NASH) and NASH-induced hepatocellular carcinoma, and provide advice on reporting practices and how to select the most appropriate model.

The authors of this Perspective argue that the commonly used terms ‘mitochondrial function’ and ‘mitochondrial dysfunction’ do not do justice to the diverse mitochondrial features, activities, functions and behaviours within cells, and thus call for the field to adopt more specific terminology in the context of mitochondrial biology.

Measurements of oxygen consumption rates have been central to the resurgent interest in studying cellular metabolism. To enhance the overall reproducibility and reliability of these measurements, Divakaruni and Jastroch provide a guide advising on the selection of experimental models and instrumentation as well as the analysis and interpretation of data.

The metabolomics literature suffers from ambiguity in the nomenclature for individual metabolites, which introduces a disconnect between publications and leads to misinterpretations. This Comment proposes recommendations for metabolite annotations to engage the scientific community and publishers to adopt a more consistent approach to metabolite nomenclature.

The environment experienced by an individual early in life has long-term health consequences. Here we summarize key factors that should be considered when designing studies in rodents that aim to address the developmental programming of metabolic disease.

In metabolic studies using rodents, body weight and food intake measurements seem easy to obtain, but several potential pitfalls can lead to erroneous data generation and interpretation. This Comment raises awareness of key conceptual and technical aspects that can increase the quality and reproducibility of this type of data.

The rapid increase in lipidomic data has triggered a community-based movement to develop guidelines and minimum requirements for generating, reporting and publishing lipidomic data. The creation of a dynamic checklist summarizing key details of lipidomic analyses using a common language has the potential to harmonize the field by improving both traceability and reproducibility.

Glucose clamps are challenging to conduct in mice and experimental approaches vary between laboratories, which complicates data interpretation and comparison of results. Here, we highlight key methodological differences and propose reporting standards for glucose clamps.

Sex as a biological variable influences almost all aspects of health and disease, yet many research studies use only males or do not consider sex differences. We describe why sex-specific reporting is needed, including in basic and animal research, and we outline recommendations for sex-specific reporting in manuscript abstracts, Methods and Results sections, tables and figures.

How to adjust metabolic rate (MR) in mice that differ in body mass and composition continues to lead to controversies. Here, the challenges that reside in the analysis of mouse MR are highlighted to spur consensus on the unequivocal use of regression-based analysis to maximize reliability and relevance of conclusions.

Bartman et al. provide a detailed review of techniques for measuring metabolic fluxes in intact mammals, how to analyse and interpret the results and how these techniques can be applied to investigate metabolism in vivo.

The two most common tests for determining metabolic health in mice are the glucose tolerance test (GTT) and insulin tolerance test (ITT). GTTs and ITTs are inexpensive and easy to perform, but how they are conducted and interpreted can radically change their meaning.

Some ‘species differences’ between mice and humans can be diminished simply by housing mice at warmer temperatures. Failure to strategically turn up the thermostat may undermine the translation of findings in mice to insights into human metabolic diseases.

Cell culture media are typically selected on the basis of common laboratory practices but have major effects on the validity, reproducibility and physiological relevance of the scientific findings. We provide arguments and quantitative examples of why choosing an appropriate cell culture medium matters, particularly in metabolic studies.

As the metabolism community has grown and diversified with scientists from multidisciplinary backgrounds, metabolic terminology has evolved and expanded. In this Comment, we reflect on this new vernacular and how established terminology can guide future discussions of metabolic research.

We are approaching the 100th anniversary of Otto Warburg’s first description of the metabolic phenotype bearing his name—a propensity for tumours to metabolize glucose anaerobically rather than aerobically, even when oxygen is available. Generations of scientists have studied the Warburg effect, yet misconceptions persist about its causes and relationship to oxidative metabolism in the mitochondria. Here, we review the definition of the Warburg effect and discuss its place within a modern understanding of cancer biology.

Mammalian cell culture represents a cornerstone of modern biomedical research. There is growing appreciation that the media conditions in which cells are cultured can profoundly influence the observed biology and reproducibility. Here, we consider a key but often ignored variable, oxygen, and review why being mindful of this environmental parameter is so important in the design and interpretation of cell culture studies.

Many commonly used inbred mouse strains carry random mutations that can affect the results of metabolic studies. Yet, awareness of such mutations as a source for experimental variation and seemingly contradictory results is lacking. It is time that scientists pay more attention to the identification, tracking and accurate reporting of mouse strains used in experiments.

Nature Metabolism is launching an online collection with articles highlighting best practices in experimental design, analysis and reporting to support the metabolic research community and increase the reproducibility of research in the life sciences.

Nature Metabolism and the Nature journals are raising the standards for reporting on sex and gender in research. Starting this June, authors will be prompted to provide details on how sex and gender were considered in study design.