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Updated: May 10, 2026
06:31
Identification and Dissection of Diverse Mouse Adipose Depots
Published on: July 11, 2019
Shox2 is a molecular determinant of depot-specific adipocyte function
Kevin Y Lee1, Yuji Yamamoto, Jeremie Boucher
1Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Summary
Short stature homeobox 2 (Shox2) regulates fat metabolism. Lower Shox2 levels in subcutaneous fat promote lipolysis and protect against obesity, influencing type 2 diabetes risk.
Area of Science:
- Adipose tissue biology
- Metabolic disease research
- Gene expression regulation
Background:
- Visceral and subcutaneous (s.c.) fat have distinct properties and differential risks for type 2 diabetes.
- Cell-autonomous gene expression differences contribute to these distinct fat depot functions.
- Short stature homeobox 2 (Shox2) is a key regulator of adipocyte function.
Purpose of the Study:
- To investigate the role of Shox2 in regulating adipocyte function and fat depot differences.
- To determine the molecular mechanisms by which Shox2 influences lipolysis and adiposity.
- To explore the therapeutic potential of targeting Shox2 for metabolic disease.
Main Methods:
- Comparative analysis of Shox2 expression in visceral and s.c. fat from rodents and humans.
- Generation of fat-specific Shox2 knockout mice.
- In vitro studies using C3H10T1/2 cells to assess Shox2 knockdown and overexpression effects.
- Analysis of beta-3 adrenergic receptor (Adrb3) expression and lipolytic rates.
- Investigation of Shox2 interaction with CCAAT/enhancer binding protein alpha (C/EBPα).
Main Results:
- Shox2 expression is higher in s.c. fat than visceral fat, and further elevated in human visceral obesity.
- Fat-specific Shox2 disruption in mice protects against diet-induced obesity, with preferential s.c. fat loss.
- Shox2 deficiency increases adipocyte beta-3 adrenergic receptor (Adrb3) expression and lipolytic rate.
- Shox2 directly interacts with C/EBPα, attenuating Adrb3 promoter activity.
Conclusions:
- Shox2 acts as a repressor of Adrb3 expression and lipolysis in adipocytes.
- Shox2 plays a critical role in establishing phenotypic differences between visceral and s.c. fat depots.
- Targeting Shox2 may offer a novel strategy for managing obesity and related metabolic disorders.
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