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Related Experiment Video

Updated: Jun 12, 2025

Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
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In vivo brown adipogenic reprogramming induced by a small molecule cocktail.

Shrute Kannappan1, Yuna Kim2, Debojyoti De3

  • 1Department of Precision Medicine, Sungkyunkwan University (SKKU) School of Medicine, Suwon, Republic of Korea; Research Center for Advanced Materials Technology, Sungkyunkwan University (SKKU), Suwon, Republic of Korea.

Biomaterials
|June 10, 2025
PubMed
Summary

Researchers developed a novel small molecule combination (SBNK) that effectively reprograms cells to brown adipocytes, offering a new strategy for obesity and diabetes treatment. This method enhances energy expenditure and improves glucose metabolism in mice.

Keywords:
Adipocyte browningBrown adipocytesCebpβ adipogenesisChemical-based in vivo reprogrammingMicroneedlePparγ adipogenesisSmall molecules

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Area of Science:

  • Metabolic research
  • Adipocyte biology
  • Therapeutic reprogramming

Background:

  • Rising prevalence of obesity and diabetes necessitates novel therapeutic strategies.
  • Brown adipose tissue (BAT) accumulation enhances energy expenditure, presenting a potential anti-obesity approach.
  • Current clinical options for inducing brown adipocyte browning are limited.

Purpose of the Study:

  • To develop a chemically induced in vivo brown adipogenic reprogramming method for therapeutic applications.
  • To identify small molecules capable of reprogramming cells into brown/beige adipocytes.
  • To evaluate the therapeutic potential of this reprogramming strategy in preclinical models.

Main Methods:

  • Phenotypic screening identified SB431542 (TGFβ inhibitor) and NKH477 (cAMP activator) combination (SBNK).
  • Reprogramming of mouse embryonic fibroblasts (MEFs) into brown/beige adipocyte-like cells.
  • In vivo studies using high-fat diet (HFD)-fed mice treated with SBNK.
  • Evaluation of local delivery efficacy using SBNK-loaded microneedle patches.

Main Results:

  • SBNK synergistically induced adipogenesis and UCP1 activation via Pparγ and Cebpβ expression.
  • SBNK treatment in HFD-fed mice enhanced browning capacity and protected against glucose metabolism impairment.
  • Local delivery via microneedle patches demonstrated a brown adipocyte browning effect.

Conclusions:

  • A novel SBNK small molecule combination effectively induces brown adipocyte reprogramming in vivo.
  • This approach shows significant therapeutic potential for metabolic diseases like obesity and diabetes.
  • The study presents a translatable strategy for brown adipocyte generation with broad clinical applicability.