# Comparative physiology and biomimetics in metabolic and environmental health: what can we learn from extreme animal phenotypes?

## TL;DR

This paper reviews how animals in extreme environments have unique metabolic traits that could help treat human metabolic diseases and highlights the need to protect these species from environmental threats.

## Contribution

The paper introduces insights from extreme animal phenotypes to identify novel therapeutic targets for human metabolic disorders.

## Key findings

- Hibernating animals like brown bears offer models for understanding reversible insulin resistance and energy homeostasis.
- Adaptations to hypoxia and metabolic aging in extreme species could lead to solutions for human diseases like obesity and diabetes.
- Environmental stressors, including climate change, threaten even the most resilient species despite their metabolic advantages.

## Abstract

This review explores the remarkable metabolic adaptations of species that thrive in extreme environments, providing insights into their resilience, flexibility and disease resistance. Species such as hibernating brown bears, migratory birds, cavefish, Greenland sharks and naked mole rats exhibit unique metabolic traits that challenge conventional paradigms of metabolic regulation. These adaptations, including resistance to hypoxia and metabolic ageing, offer potential solutions to human metabolic disorders, including obesity, type 2 diabetes and CVD. Insights from comparative physiology, particularly the mechanisms by which animals cope with food scarcity, extreme temperatures and hypoxia, could help identify novel therapeutic targets for advancing human health. For example, hibernation can serve as a model for understanding metabolic diseases, providing insights into reversible insulin resistance and energy homeostasis. This review also highlights the impact of environmental stressors, including climate change, on these species, which may jeopardise their survival despite their resilience. Accelerating anthropogenic environmental change threatens even the most resilient animal species. We call for a holistic approach to conservation and environmental protection to preserve these species and the valuable lessons they offer for managing our metabolic health.

The online version contains a slideset of the figures for download available at 10.1007/s00125-025-06611-3.