Researchers uncover the molecular mechanisms underlying sex-specific calorie burning in BAT. Credit score: Institute of Science Tokyo
Larger exercise of PGC-1α permits brown fats cells in females to realize thermogenic exercise and power expenditure in comparison with males, reveals a examine performed in Japan. This analysis demonstrates that PGC-1α protein promotes phospholipid synthesis, which strengthens mitochondria of brown fats cells and enhances their heat-generating capability in feminine mice. The findings reveal a female-specific mechanism of power metabolism, boosted by PGC-1α and estrogen, which may encourage new therapies for the prevention of weight problems and diabetes.
Weight problems is a serious international well being concern, contributing to diabetes and a spread of metabolic issues. Apparently, whereas weight problems impacts each sexes, girls are usually much less liable to obesity-related diabetes and cardiovascular illnesses, in comparison with males.
Whereas the organic causes for this distinction should not absolutely understood, one potential issue is brown adipose tissue (BAT)—a specialised fats tissue that dissipates power as warmth to keep up physique temperature. Earlier research have proven that BAT is extra metabolically energetic in females than in males, however the actual molecular mechanism has remained unclear.
To handle this query, a analysis staff from the Institute of Science Tokyo, Japan, got down to examine the mechanism underlying the sex-specific exercise of BAT.
The staff was led by Assistant Professor Kazutaka Tsujimoto, graduate college students Akira Takeuchi and Jun Aoki, and Professor Tetsuya Yamada from the Division of Molecular Endocrinology and Metabolism, Graduate College of Medical and Dental Sciences, Science Tokyo, in collaboration with Affiliate Professor Nozomu Kono, Assistant Professor Kuniyuki Kano, and Professor Junken Aoki from the College of Tokyo. The findings have been printed within the journal Nature Communications on July 14, 2025.
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a key regulator of power metabolism and mitochondrial exercise, present in tissues together with brown fats, coronary heart, skeletal muscle, and mind.
“PGC-1α is a master regulator of mitochondrial function in BAT,” explains Yamada and Tsujimoto. “So, to uncover the sex-specific mechanism of BAT, we focused on the activity of PGC-1α.”
Utilizing genetically modified mice that lacked PGC-1α protein solely in BAT cells, the staff in contrast the female and male mice with multi-omics approaches, together with transcriptomics (to evaluate gene expression), metabolomics (to investigate power metabolites), and lipidomics (to profile lipid composition) to elucidate the protein’s position intimately.
In response to the outcomes, eradicating PGC-1α impaired BAT thermogenesis solely in feminine mice, as evidenced by their decrease physique temperature throughout chilly publicity. Moreover, they confirmed decreased oxygen consumption, and their mitochondria had fewer and fewer organized cristae—the interior folds the place power manufacturing happens.
Molecular profiling revealed key insights into this mechanism: PGC-1α prompts genes concerned in de novo lipogenesis (DNL), partially by carbohydrate-response element-binding protein beta (ChREBPβ)—a transcription issue that regulates expression of DNL-related genes. This pathway boosts the manufacturing of sure phospholipids, together with ether-linked phosphatidylethanolamine and cardiolipin, that are important for sustaining mitochondrial construction and performance. With out these lipids, mitochondria change into much less environment friendly, lowering the tissue’s skill to generate warmth.
Notably, the PGC-1α–ChREBPβ lipid synthesis pathway was additional enhanced by estrogen signaling, which elevated the expression of lipid metabolism-related genes in feminine BAT.
“This coordination between PGC-1α and estrogen explains why female BAT outperforms male BAT in energy expenditure,” says Yamada and Tsujimoto. “It could also be an entirely new target for therapies to enhance lipid metabolism.”
To help this, the researchers performed further experiments exhibiting that suppressing ChREBPβ in feminine BAT reproduced the identical mitochondrial defects and decreased thermogenesis noticed with PGC-1α deletion. This impact was not noticed in males, highlighting the sex-specific attribute of the mechanism.
General, the examine gives new perception into how organic intercourse shapes power metabolism—figuring out PGC-1α-mediated phospholipid synthesis as a key regulator of BAT thermogenesis. Stimulating this pathway may promote power expenditure, enhance metabolic well being, and forestall weight problems and sort 2 diabetes. The findings set the stage for brand spanking new interventions primarily based on metabolic mechanisms, paving the way in which towards a more healthy future.
Extra data:
Akira Takeuchi et al, Intercourse distinction in BAT thermogenesis is dependent upon PGC-1α–mediated phospholipid synthesis in mice, Nature Communications (2025). DOI: 10.1038/s41467-025-61219-w
Offered by
Institute of Science Tokyo
Quotation:
Feminine-specific mechanism for power expenditure found in brown adipose tissue (2025, September 11)
retrieved 11 September 2025
from https://medicalxpress.com/information/2025-09-female-specific-mechanism-energy-expenditure.html
This doc is topic to copyright. Other than any truthful dealing for the aim of personal examine or analysis, no
half could also be reproduced with out the written permission. The content material is offered for data functions solely.
