Related Experiment Video
Updated: May 17, 2026
06:08
Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
Published on: May 19, 2023
Consecutive positive feedback loops create a bistable switch that controls preadipocyte-to-adipocyte conversion.
Byung Ouk Park1, Robert Ahrends, Mary N Teruel
1Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Cell Reports
|October 16, 2012
Summary
Adipogenesis involves an irreversible switch, triggered by specific signals, that locks cells into a fat-accumulating state. Positive feedback loops ensure this commitment, with insulin then controlling the degree of fat storage.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Adipogenesis is crucial for vertebrate weight maintenance.
- The precise mechanism and timing of the irreversible transition to lipid-accumulating adipocytes remain unclear.
Purpose of the Study:
- To elucidate the regulatory mechanism governing the irreversible transition during adipogenesis.
- To identify the molecular players and feedback loops involved in cell fate commitment.
Main Methods:
- Single-cell fluorescence imaging was employed to observe cellular changes.
- Mathematical modeling was used in conjunction with experimental data.
Main Results:
- An all-or-none switch precedes lipid accumulation in adipogenesis.
- Glucocorticoid and cAMP signals initiate the process by elevating C/EBPβ levels.
- Three sequential positive feedback loops (PPARγ → C/EBPα → C/EBPβ → insulin receptor) establish a robust, irreversible differentiation state.
- Insulin regulates fat accumulation in a graded manner after the differentiation switch is activated.
Conclusions:
- A novel regulatory motif involving sequential positive feedback loops locks cells into a terminally differentiated adipocyte state.
- This mechanism ensures commitment by rejecting transient or weak differentiation stimuli.
- Understanding this switch is key to comprehending fat cell development and weight regulation.
Related Concept Videos
01:07Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
01:18Positive and Negative Feedback Loops
Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires maintaining an internal dynamic equilibrium:
01:01Feedback Loops
In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...