Several factors inhibit lipolysis, the process of breaking down stored fat. The most significant inhibitor is insulin. Insulin promotes fat storage and reduces the breakdown of fats. Other inhibitors include:
Key Inhibitors of Lipolysis
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Insulin: This hormone is a major regulator of metabolism. It stimulates lipid synthesis (fat creation) and storage, while simultaneously decreasing the release of free fatty acids (FFAs) from fat cells. This directly inhibits lipolysis. [¹][²][³] As stated in one study, "One of the basic functions of insulin in the body is to inhibit lipolysis in adipocytes." [³] Another study highlights insulin's role in the "anti-lipolysis process" in adipose tissue. [²]
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Lactate: This metabolic byproduct activates GPR81, an orphan G-protein-coupled receptor found in fat cells. This activation leads to a reduction in lipolysis. [⁴][⁵][⁶] One study showed that lactate inhibits palmitate lipolysis by 30%. [⁷]
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Adenosine: This molecule, released by adipocytes (fat cells), acts locally to suppress lipolysis. [⁸]
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B cells (in specific conditions): An age-related increase in B cells can promote inflammation and inhibit lipolysis in adipose tissue, particularly during sepsis. [⁹]
Understanding the Mechanisms
The inhibition of lipolysis by these factors occurs through different pathways, often involving interactions with receptors and intracellular signaling cascades. These complex interactions regulate the activity of key enzymes involved in fat breakdown. For example, insulin's impact on lipolysis is directly tied to its influence on enzymes like hormone-sensitive lipase (HSL).
Pharmacological Inhibitors
Researchers are also exploring small molecule inhibitors that specifically target enzymes involved in lipolysis, like ATGL (adipose triglyceride lipase). These offer potential avenues for therapeutic intervention, though their widespread use is still under development. [¹⁰]
[¹]: Information from the provided text stating Insulin is the most important hormone that inhibits lipolysis.
[²]: Anti-Lipolysis Induced by Insulin in Diverse Pathophysiologic ... https://pmc.ncbi.nlm.nih.gov/articles/PMC7227813/
[³]: Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily ... https://pmc.ncbi.nlm.nih.gov/articles/PMC3753874/
[⁴]: Lactate inhibits lipolysis in fat cells through activation of an orphan G ... https://pubmed.ncbi.nlm.nih.gov/19047060/
[⁵]: Lactate Inhibits Lipolysis in Fat Cells through Activation of an ... https://www.sciencedirect.com/science/article/pii/S0021925819818458
[⁶]: 1660-P: Lactate Inhibits Lipolysis in Healthy Males—A Randomized ... https://dx.doi.org/10.2337/db23-1660-P
[⁷]: 1660-P: Lactate Inhibits Lipolysis in Healthy Males—A Randomized ... https://dx.doi.org/10.2337/db23-1660-P
[⁸]: Lipolysis - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/immunology-and-microbiology/lipolysis
[⁹]: Age-associated accumulation of B cells promotes macrophage ... https://pubmed.ncbi.nlm.nih.gov/38492219/
[¹⁰]: Small-Molecule Inhibitors Targeting Lipolysis in Human Adipocytes ... https://pubs.acs.org/doi/full/10.1021/jacs.1c10836
