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The multiple roles of life stress in metabolic disorders

Nature Reviews Endocrinology volume 19, pages 10–27 (2023)Cite this article

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Abstract

The activation of stress-related neuroendocrine systems helps to maintain homeostasis, but excessive stress can damage body functions. We review current evidence from basic sciences and epidemiology linking stress to the development and progression of metabolic disorders throughout life. Findings from rodents demonstrate that stress can affect features of metabolic dysfunction, such as insulin resistance, glucose and lipid homeostasis, as well as ageing processes such as cellular senescence and telomere length shortening. In human studies, stressors in the home, workplace and neighbourhood are associated with accelerated ageing and metabolic and immune alterations, both directly and indirectly via behavioural risks. The likelihood of developing clinical conditions, such as diabetes mellitus and hepatic steatosis is increased in individuals with adverse childhood experiences or long-term (years) or severe stress at work or in private life. The increased risk of metabolic disorders is often associated with other stress-related conditions, such as mental health disorders, cardiovascular disease and increased susceptibility to infections. Equally, stress can worsen prognosis in metabolic diseases. As favourable modifications in stressors are associated with reductions in incidence of metabolic disorders, further investigation of the therapeutic value of targeting stress in personalized medicine is warranted.

Key points

  • Both animal and human research suggests that stress and related changes in sympathetic–parasympathetic balance and the hypothalamic–pituitary–adrenal axis can accelerate biological ageing, including unfavourable changes in metabolism and immune function.

  • The adverse impact on metabolic disease risk in adults with a history of childhood adversity is potentiated by mental disorders and behavioural risks and the risk of metabolic disease can be more than twofold higher than in adults without childhood adversity.

  • In adults, stress is associated with a 1.1-fold to 1.4-fold excess risk of obesity, diabetes mellitus and liver disease.

  • The excess risk for mental disorders, such as depression, and cardiovascular disease among individuals with stress in adulthood is slightly higher than that for obesity, diabetes mellitus and liver disease.

  • Life stress is also a prognostic factor in patients, accelerating the transition of metabolic diseases towards multimorbidity, frailty and death.

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Fig. 1: Mechanisms of stress-induced metabolic changes.
Fig. 2: Preclinical metabolic changes from childhood to adulthood in individuals exposed to stressors at the individual and community levels and with stress appraisal.
Fig. 3: Disease trajectories, multimorbidity and death in individuals exposed to socioeconomic stressors at the individual and community levels.

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Acknowledgements

M.K. was supported by the UK Medical Research Council (S011676), Wellcome Trust, UK (221854/Z/20/Z), National Institute on Aging (NIH), US (R01AG056477), and the Academy of Finland (350426). A.B. was supported by NIH/NIDDK (DK117504, DK118150, DK102496), NIH/NHLBI (HL151740), NIH/NIA (AG043972) and MN Partnership for Biotechnology and Molecular Genomic #18.4. I.K. was supported by National Institute on Aging (R01 AG042463).

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Authors and Affiliations

  1. Department of Mental Health of Older People, Faculty of Brain Sciences, University College London, London, UK

    Mika Kivimäki

  2. Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    Mika Kivimäki

  3. Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA

    Alessandro Bartolomucci

  4. Department of Medicine, University of Parma, Parma, Italy

    Alessandro Bartolomucci

  5. Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Ichiro Kawachi

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Glossary

Allostatic states

An allostatic state is a state in which there is a chronic deviation of regulatory systems away from their normal state of operation.

Burnout

A syndrome resulting from excessive or prolonged stress and characterized by feelings of energy depletion or exhaustion, increased mental distancing, or feelings of negativism or cynicism related to one’s job and reduced professional efficacy.

Ultradian

A rhythm with a period of recurrence shorter than 24 h.

Polysomnography

A test protocol monitoring multiple physiological changes that occur during sleep (such as brain waves, eye and leg movement, heart rate and breathing) to study sleep and diagnose sleep disorders.

Stroop colour–word interference task

A neuropsychological test to assess the ability to inhibit cognitive inference (a mismatch between the name of a colour and the colour it is printed on) used in the laboratory to induce stress in a study participant.

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Kivimäki, M., Bartolomucci, A. & Kawachi, I. The multiple roles of life stress in metabolic disorders. Nat Rev Endocrinol 19, 10–27 (2023). https://doi.org/10.1038/s41574-022-00746-8

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