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White adipocytes in subcutaneous fat depots require KLF15 for maintenance in preclinical models
Liang Li, Brian J. Feldman
Liang Li, Brian J. Feldman
Published July 1, 2024
Citation Information: J Clin Invest. 2024;134(13):e172360. https://doi.org/10.1172/JCI172360.
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Research Article Cell biology Endocrinology Article has an altmetric score of 443

White adipocytes in subcutaneous fat depots require KLF15 for maintenance in preclinical models

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Abstract

Healthy adipose tissue is essential for normal physiology. There are 2 broad types of adipose tissue depots: brown adipose tissue (BAT), which contains adipocytes poised to burn energy through thermogenesis, and white adipose tissue (WAT), which contains adipocytes that store lipids. However, within those types of adipose, adipocytes possess depot and cell-specific properties that have important implications. For example, the subcutaneous and visceral WAT confers divergent risk for metabolic disease. Further, within a depot, different adipocytes can have distinct properties; subcutaneous WAT can contain adipocytes with either white or brown-like (beige) adipocyte properties. However, the pathways that regulate and maintain this cell and depot-specificity are incompletely understood. Here, we found that the transcription factor KLF15 is required for maintaining white adipocyte properties selectively within the subcutaneous WAT. We revealed that deletion of Klf15 is sufficient to induce beige adipocyte properties and that KLF15’s direct regulation of Adrb1 is a critical molecular mechanism for this process. We uncovered that this activity is cell autonomous but has systemic implications in mouse models and is conserved in primary human adipose cells. Our results elucidate a pathway for depot-specific maintenance of white adipocyte properties that could enable the development of therapies for obesity and associated diseases.

Authors

Liang Li, Brian J. Feldman

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Figure 2

Adipocyte-specific Klf15 KO promotes beige adipocyte formation in iWAT.

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Adipocyte-specific Klf15 KO promotes beige adipocyte formation in iWAT.
...
(A) RT-qPCR quantifying the expression levels of Klf15 in iWAT, gWAT, BAT, and liver from WT and Adipo-Klf15 mice. Student’s t tests followed by Holm-Šidák correction, n = 3. (B) RT-qPCR quantifying the expression levels of Klf15 in the SVF and adipocyte fraction of iWAT from WT and Adipo-Klf15 mice. Student’s t test followed by Holm-Šidák correction, n = 3. (C) Representative images of in situ iWAT in WT and Adipo-Klf15 mice. Scale bar: 5 mm. (D) Quantification of iWAT mass as a percent of body weight in WT and Adipo-Klf15 littermates. Ratio paired t test, n = 5. (E) RT-qPCR quantifying the expression levels of thermogenic genes in iWAT of WT and Adipo-Klf15 littermates. Student’s t test, n = 5. (F–H) RT-qPCR quantifying the expression levels of adrenergic receptors in iWAT, gWAT, and BAT from WT and Adipo-Klf15 mice. Student’s t test followed by Holm-Šidák correction, n = 5. (I) RT-qPCR quantifying the expression levels of Adrb1 versus Adrb3 in iWAT in littermates of WT and Adipo-Klf15 mice. 1-tailed ratio paired t test, n = 4. (J) Immunoblots detecting the levels of β1AR protein in iWAT from WT and Adipo-Klf15 mice compared with the levels of β-actin controls. (K) Quantifying the relative protein level of β1AR. Student’s t test, n = 4. *P < 0.05, **P < 0.01, ***P < 0.001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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