Human adipose beiging in response to cold and mirabegron

JCI Insight, 2018 · DOI: https://doi.org/10.1172/jci.insight.121510 · Published: August 9, 2018

Simple Explanation

The study investigates how human fat tissue responds to cold and a drug called mirabegron, focusing on a process called "beiging" where white fat cells start acting more like brown fat cells which burn energy. Researchers applied ice packs to the thighs or abdomens of lean and obese participants for 10 days and examined the fat tissue for changes in specific markers related to beiging, like UCP1 and TMEM26. They also treated obese participants with mirabegron for 10 weeks to see if the drug could induce a similar beiging effect, potentially offering a way to improve metabolism in obese individuals.

Study Duration

10 days (cold exposure), 10 weeks (mirabegron)

Participants

Lean and obese human subjects

Evidence Level

Not specified

Key Findings

1
Repeated cold exposure upregulates UCP1 and TMEM26 protein expression in subcutaneous white adipose tissue (WAT) in both lean and obese subjects.
2
Cold exposure resulted in a "crossover effect," where the non-iced leg also showed increased UCP1 protein, suggesting a systemic response mediated by the sympathetic nervous system (SNS).
3
Chronic treatment with mirabegron in obese subjects induced UCP1, TMEM26, and CIDEA expression, indicating that β3-adrenergic receptor activation can promote beiging in human subcutaneous WAT.

Research Summary

This study demonstrates that cold exposure and mirabegron treatment can induce beiging of human subcutaneous WAT. The beiging response to cold was not inhibited in obese or older subjects, suggesting that this approach could be exploited therapeutically in individuals with metabolic disease. Mirabegron treatment increased the expression of beige adipose markers, but did not induce PGC1α, which may limit the full potential of the beiging process.

Practical Implications

Therapeutic Potential

The induction of beige adipose tissue in humans via cold exposure or β3 agonists like mirabegron may be a viable strategy to improve glucose and lipid metabolism, particularly in older, insulin-resistant, obese individuals.

Sympathetic Nervous System Activation

The crossover effect observed with cold exposure suggests that even localized cooling can activate the SNS, leading to systemic effects on adipose tissue beiging.

Targeting Adipose Tissue

The study highlights the potential of subcutaneous WAT to undergo beiging, offering a new avenue for therapies aimed at combating metabolic disorders.

Study Limitations

1
The study did not determine whether adipose beiging and mirabegron treatment are related to improved glucose and lipid homeostasis.
2
The study did not include a paired study design to detect seasonal changes in mitochondrial bioenergetics.
3
The failure to induce PGC1α by mirabegron treatment in obese subjects may limit the beiging process.

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