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Updated: Oct 22, 2025

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Bird evolution by insulin resistance
1Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan.
Atmospheric oxygen changes drove vertebrate evolution. Theropods adapted to low oxygen by losing genes for insulin sensitivity, becoming insulin resistant and hyperathletic, while later adapting to high oxygen by developing antioxidant defenses.
Area of Science:
- Evolutionary Biology
- Paleontology
- Physiology
Background:
- Atmospheric oxygen levels have fluctuated throughout Earth's history, significantly impacting vertebrate evolution.
- The Permian-Triassic boundary experienced a severe oxygen drop, posing a major challenge to vertebrate life.
- Later increases in oxygen during the Jurassic, Cretaceous, and Tertiary periods presented new evolutionary pressures.
Purpose of the Study:
- To investigate the evolutionary adaptations of theropods in response to changing atmospheric oxygen concentrations.
- To explore the genetic and physiological mechanisms underlying theropod adaptation to both hypoxic and hyperoxic environments.
- To understand how these adaptations influenced theropod competitiveness and diversification.
Main Methods:
- Comparative genomics to identify gene losses in theropod genomes (e.g., omentin, GLUT4).
- Physiological analysis to understand insulin resistance and hyperathleticism in theropods.
- Examination of genetic pathways related to reactive oxygen species (ROS) defense in Neoaves (e.g., NRF2, KEAP1).
Main Results:
- Theropods lost genes for insulin sensitivity (omentin, GLUT4), leading to insulin resistance and enhanced athletic performance under hypoxia.
- Some theropods increased body size to mitigate ROS leakage during periods of high oxygen.
- Neoaves evolved constitutively active NRF2 due to KEAP1 C-terminal deletion, enabling robust antioxidant defenses against ROS.
Conclusions:
- Theropod adaptations to oxygen fluctuations were crucial for their evolutionary success, including outcompeting mammals in the Triassic.
- Insulin resistance and antioxidant systems represent key evolutionary solutions to environmental oxygen challenges.
- Genetic modifications in theropods, such as NRF2 activation, highlight the power of molecular adaptations in shaping vertebrate evolution.
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