Related Experiment Video
Updated: Aug 1, 2025
Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
Live-cell imaging identifies cAMP microdomains regulating β-adrenoceptor-subtype-specific lipolytic responses in
Kirstie A De Jong1, Sandra Ehret2, Joerg Heeren2
1Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract:
Lipolysis of stored triglycerides is stimulated via β-adrenergic receptor (β-AR)/3',5'-cyclic adenosine monophosphate (cAMP) signaling and inhibited via phosphodiesterases (PDEs). In type 2 diabetes, a dysregulation in the storage/lipolysis of triglycerides leads to lipotoxicity. Here, we hypothesize that white adipocytes regulate their lipolytic responses via the formation of subcellular cAMP microdomains. To test this, we investigate real-time cAMP/PDE dynamics at the single-cell level in human white adipocytes with a highly sensitive florescent biosensor and uncover the presence of several receptor-associated cAMP microdomains where cAMP signals are compartmentalized to differentially regulate lipolysis. In insulin resistance, we also detect cAMP microdomain dysregulation mechanisms that promote lipotoxicity, but regulation can be restored by the anti-diabetic drug metformin. Therefore, we present a powerful live-cell imaging technique capable of resolving disease-driven alterations in cAMP/PDE signaling at the subcellular level and provide evidence to support the therapeutic potential of targeting these microdomains.
Insights
White adipocytes use cAMP microdomains to control fat breakdown. In type 2 diabetes, these microdomains are dysregulated, causing lipotoxicity, but metformin can restore their function.
Area of Science:
- Cell biology
- Metabolic signaling
- Endocrinology
Background:
- Lipolysis is regulated by β-adrenergic receptor (β-AR)/cAMP signaling and phosphodiesterases (PDEs).
- Type 2 diabetes involves triglyceride dysregulation and lipotoxicity.
- Subcellular compartmentalization of signaling molecules is crucial for cellular function.
Purpose of the Study:
- To investigate the role of subcellular cAMP microdomains in regulating lipolysis in human white adipocytes.
- To examine cAMP/PDE dynamics in insulin resistance and type 2 diabetes.
- To assess the therapeutic potential of targeting cAMP microdomains.
Main Methods:
- Utilized a sensitive fluorescent biosensor for real-time, single-cell imaging of cAMP/PDE dynamics.
- Studied human white adipocytes under basal and stimulated conditions.
- Investigated the effects of insulin resistance and metformin treatment.
Main Results:
- Identified distinct, receptor-associated cAMP microdomains in white adipocytes that compartmentalize cAMP signals.
- Demonstrated that these microdomains differentially regulate lipolysis.
- Observed dysregulation of cAMP microdomains in insulin resistance, contributing to lipotoxicity.
- Showed that metformin can restore normal cAMP microdomain function.
Conclusions:
- White adipocytes employ cAMP microdomains to precisely control lipolysis.
- Dysregulation of these microdomains contributes to lipotoxicity in insulin resistance.
- Targeting cAMP microdomains represents a potential therapeutic strategy for type 2 diabetes, with metformin showing efficacy.
More Related Videos
06:35Author Spotlight: Insights into Cardiometabolic Diseases with Subcutaneous Adipose Tissue Microvasculature Studies
Published on: April 5, 2024
04:46Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
