Year in Review

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  • Metabolites have emerged as central regulators of biological function, but understanding mechanisms of metabolite regulation has proven challenging. In 2021 we have seen discoveries in the field of metabolite signalling motivated by a combination of scientific intuition and the elegant deployment of new technologies.

    • Edward T. Chouchani
    Year in Review
  • In 2021, several discoveries shed light on the pathomechanisms of β-cell failure during the initiation and progression of diabetes mellitus, and validated novel molecular targets for intervention. Moreover, the field of stem-cell-derived replacements for β-cells is rapidly advancing. These advances bring us closer to therapies to protect and/or regenerate β-cell mass.

    • Mostafa Bakhti
    • Heiko Lickert
    Year in Review
  • Physical activity stimulates tissue crosstalk and provides powerful protection against cardiometabolic disease. This past year, several studies have expanded our knowledge of the secreted molecules regulated by physical activity, uncovered new circuits of cell and tissue crosstalk and provided fundamental insights into the mechanisms that underlie the cardiometabolic benefits of exercise.

    • Jonathan Z. Long
    Year in Review
  • Obesity and impaired metabolic health are important risk factors for severe COVID-19. Novel data indicate that these risk factors might also promote vaccine-breakthrough SARS-CoV-2 infections in fully vaccinated people. Here, these relationships are discussed and post-acute sequelae of COVID-19 that are related to obesity and impaired metabolic health are addressed.

    • Norbert Stefan
    Year in Review
  • In 2021, clinical trials reported the promising effects of incretins and a new class of dual glucagon-like peptide 1–glucose-dependent insulinotropic peptide receptor agonists in preventing and treating type 2 diabetes mellitus and obesity. These ‘twincretins’ will transform the prevention of obesity and type 2 diabetes mellitus and the care of people with these conditions.

    • Elaine Chow
    • Juliana C. N. Chan
    Year in Review
  • Neuroendocrine neoplasms are derived from the diffuse endocrine system and represent a spectrum of tumours with a diverse range of molecular abnormalities, functionality and anatomical locations. Here, some key advances in molecular diagnosis, functional imaging and therapeutic strategies that have been published in 2020 are discussed.

    • Martyn E. Caplin
    • Gowri M. Ratnayake
    Year in Review
  • Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by reproductive and metabolic disturbances. Androgen excess is a hallmark of PCOS, driving many of the phenotypic features. In 2020, several findings highlight altered metabolic pathways as an underlying biological mechanism in PCOS. These findings add to our understanding of the complex interaction between metabolic homeostasis and reproduction.

    • Jenny A. Visser
    Year in Review
  • Heart failure and chronic kidney disease are frequent causes of morbidity and mortality in people with type 2 diabetes mellitus. Cardiovascular outcome trials have confirmed benefits of sodium–glucose co-transporter 2 inhibitors on cardiovascular events, cardiovascular deaths, hospitalization for heart failure and renal outcomes. These benefits now extend to people with and without type 2 diabetes mellitus.

    • Kamlesh Khunti
    Year in Review
  • Owing to the strong association of non-alcoholic fatty liver disease with obesity and cardiometabolic disease, in 2020 experts controversially proposed to rename this condition as ‘metabolic associated fatty liver disease’. Additional studies have elucidated new genetic and dietary modifiers of this disease. This knowledge is essential to improve diagnosis, risk-stratification and treatment.

    • Mark A. Herman
    Year in Review
  • The development and application of effective immunotherapies for type 1 diabetes mellitus has lagged behind our ability to identify and stage individuals in pre-clinical stages of disease. This Year in Review addresses advances in immunotherapy aimed towards prevention and our readiness to roll out screening in the broader population.

    • Anette-G. Ziegler
    • Ezio Bonifacio
    Year in Review
  • Metabolic diseases emerged as important risk factors for severe COVID-19, but the mechanisms responsible remained unclear for some time. The severity of metabolic diseases was also associated with worse outcomes in patients with COVID-19, forcing clinicians to adjust their thinking on which patients with metabolic disease, but without COVID-19, to prioritize for treatment during and immediately after the pandemic.

    • Carel W. le Roux
    Year in Review
  • Personalized, or precision, medicine in type 2 diabetes mellitus is becoming a reality with new insights into the contributions of subgroup analyses. The roadmap to future implementation must take into account individual and subgroup variability in genetic architecture, environment, clinical measures, lifestyle, cost-effectiveness and treatment burden.

    • Louis H. Philipson
    Year in Review
  • Multikinase inhibitors are effective treatments for thyroid cancers, acting primarily as antiangiogenic agents. This year, advances have been made in selective targeting of RET and BRAF in patients with medullary and anaplastic thyroid cancers, respectively. However, Hürthle cell carcinomas have a unique genomic landscape with no dominant truncal drivers, precluding simplistic approaches to therapeutic targeting.

    • Vera Tiedje
    • James A. Fagin
    Year in Review
  • Feeding is regulated by defined neuronal pathways and circulating factors that ensure homeostatic balance is maintained. However, many emotion-affective pathways are also involved in communicating positive and negative valence on feeding behaviour. In 2019, several seminal discoveries were made that illuminate the complex interaction between homeostatic and hedonic feeding control mechanisms.

    • Herbert Herzog
    Year in Review
  • Pancreatic islets, which are critical for glucose homeostasis, are endocrine microorgans embedded in the exocrine pancreas; their location has often limited studying their function. In 2019, advances in islet biology were achieved with new technologies extending findings from several decades ago and with conceptual advances built on findings from other fields.

    • Susan Bonner-Weir
    Year in Review
  • Exercise is a potent modulator of intestinal microbiota composition and function. In 2019, several studies uncovered biologically important links between skeletal muscle and the gut microbiota, revealing how the gut bacteria respond to an exercise challenge and have reciprocal roles in fuel availability, muscle function and endurance performance.

    • John A. Hawley
    Year in Review
  • A key component in the development from fatty liver to hepatocellular carcinoma (HCC) is the appearance of nonalcoholic steatohepatitis (NASH). The precise cellular processes that trigger the advancement of NASH towards HCC are not well understood. In 2018, three key papers were published that help us better understand these processes.

    • Saskia Reibe
    • Mark A. Febbraio
    Year in Review
  • In 2018, more than 4,000 publications were dedicated to the study of the gut microbiota, and an important proportion investigated cardiometabolic disorders associated with overweight and obesity. Novel mechanisms and strategies have emerged, some of which were focused not only on specific bacteria or nutrients, but also on new metabolites.

    • Patrice D. Cani
    Year in Review
  • Circadian rhythm research is beginning to show how rhythms sustain health. Genome-wide transcriptome, metabolome and proteome studies have improved our understanding of circadian regulation. This knowledge is leveraged for behavioural interventions that optimize daily rhythms, the timing of drug delivery and the targeting of clock components to prevent or treat chronic diseases.

    • Satchidananda Panda
    Year in Review
  • Cancer cells consume and utilize glucose at a higher rate than normal cells. However, some microenvironments limit the availability of nutrients and glucose. In 2018, researchers found that tumours depend on a variety of different nutrient sources, both locally and systemically, to overcome metabolic limitations and promote tumour progression and metastasis.

    • Alexander R. Terry
    • Nissim Hay
    Year in Review