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Updated: Jun 17, 2026

Determining Basal Energy Expenditure and the Capacity of Thermogenic Adipocytes to Expend Energy in Obese Mice
Published on: November 11, 2021
Copper import via CTR1 supports the β3-Adrenergic thermogenic program
Tae-Il Jeon1, Young-Seung Lee2, Tamara Korolnek3
1Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA; Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea.
Copper importer CTR1 is crucial for adaptive thermogenesis. Cold and beta3-adrenergic receptor stimulation increase copper, essential for energy expenditure and preventing hypothermia.
Area of Science:
- Metabolic regulation
- Mitochondrial function
- Adipose tissue biology
Background:
- Adaptive thermogenesis relies on coordinated mitochondrial oxidation and metabolic shifts.
- The precise signals coordinating these processes remain unclear.
Purpose of the Study:
- Investigate the role of copper importer CTR1 in adaptive thermogenesis.
- Determine how CTR1 influences energy expenditure and thermogenic capacity.
Main Methods:
- Utilized adipocyte-specific Ctr1 knockout (ACKO) mice and brown adipose tissue-specific Ctr1 knockout (BCKO) mice.
- Performed proteomic analysis of brown adipose tissue.
- Assessed energy expenditure, cold tolerance, and lipolytic activation.
Main Results:
- Cold exposure and beta3-adrenergic receptor (β3-AR) stimulation upregulate CTR1 and copper (Cu) in thermogenic adipose tissues.
- ACKO mice showed reduced energy expenditure and severe hypothermia.
- Cu deficiency impaired oxidative phosphorylation, thermogenic programs, and lipolytic activation, including HSL phosphorylation.
Conclusions:
- CTR1-dependent copper import is an inducible part of the β3-adrenergic thermogenic program.
- Intracellular copper availability is a key factor in thermogenic capacity during adaptive thermogenesis.
- Elesclomol treatment partially restored mitochondrial function and improved cold tolerance in ACKO mice.
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