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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Deletion of Letmd1 leads to the disruption of mitochondrial function in brown adipose tissue
Runjie Song1, Yaqi Du1, Peng Li1
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Abstract:
Human cervical cancer oncogene (HCCR-1), also named as LETMD1, is an LETM-domain containing outer mitochondrial membrane protein which plays an important role in carcinogenesis. The present study found that the loss of Letmd1 in mice led to severe abnormities, such as brown adipose tissue (BAT) whitening, impaired thermogenesis of both BAT and beige fat, cold intolerance, diet-induced obesity, glucose intolerance and insulin resistance. Mechanically, the deletion of Letmd1 in BAT caused decreased level of both mitochondrial and intracellular Ca2+. The reduced intracellular Ca2+ could suppress the fission of mitochondria and ultimately lead to the disruption of BAT thermogenesis by regulating mitochondrial structures and functions. This study indicates that LETMD1 played a crucial role in BAT thermogenesis and energy homeostasis through regulating mitochondrial structures and functions, which provides a novel insight into therapeutic target exploration from oncogenes for metabolic disorders.
Insights
Loss of the human cervical cancer oncogene (HCCR-1), LETMD1, impairs brown fat thermogenesis and energy balance. This discovery offers new therapeutic targets for metabolic disorders.
Area of Science:
- Mitochondrial biology
- Metabolic disorders
- Oncogene function
Background:
- Human cervical cancer oncogene (HCCR-1), also known as LETMD1, is an outer mitochondrial membrane protein implicated in carcinogenesis.
- LETMD1's role in metabolic regulation and energy homeostasis is not fully understood.
Purpose of the Study:
- To investigate the function of Letmd1 in metabolic regulation, specifically in brown adipose tissue (BAT) thermogenesis.
- To elucidate the molecular mechanisms by which Letmd1 influences mitochondrial function and energy balance.
Main Methods:
- Generation of Letmd1-deficient mice.
- Analysis of brown adipose tissue (BAT) and beige fat characteristics.
- Assessment of thermogenesis, glucose tolerance, and insulin resistance.
- Measurement of intracellular and mitochondrial calcium levels.
- Evaluation of mitochondrial structure and function.
Main Results:
- Loss of Letmd1 in mice resulted in BAT whitening, impaired thermogenesis in BAT and beige fat, cold intolerance, obesity, glucose intolerance, and insulin resistance.
- Deletion of Letmd1 in BAT led to decreased mitochondrial and intracellular calcium levels.
- Reduced intracellular calcium suppressed mitochondrial fission, disrupting BAT thermogenesis via altered mitochondrial structure and function.
Conclusions:
- LETMD1 is essential for maintaining BAT thermogenesis and overall energy homeostasis.
- LETMD1 regulates mitochondrial calcium levels, impacting mitochondrial dynamics and function.
- LETMD1 represents a potential therapeutic target for metabolic disorders, repurposing insights from cancer oncogenes.
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