Lipid Metabolism Regulation in Adipose Tissue

Adipose tissue functions as a highly dynamic organ that balances lipid storage with fatty acid mobilisation to meet systemic energy demands. Triglycerides are deposited in specialised organelles known as lipid droplets and are hydrolysed through the coordinated action of lipolytic enzymes. Hormonal cues—principally insulin, catecholamines and glucagon—phosphorylate regulatory proteins to switch between anabolic pathways (lipogenesis) and catabolic pathways (lipolysis). Key enzymes such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) initiate and sustain triglyceride breakdown, respectively, while proteins like perilipin 1 modulate access of lipases to lipid stores. Beyond classical cytosolic lipolysis, emerging evidence highlights autophagic and lysosomal routes and cell-intrinsic nutrient-sensing mechanisms that fine-tune fatty acid release. Dysregulation of these processes is implicated in obesity, insulin resistance and steatotic liver disease, making adipose lipid metabolism a critical focus for therapeutic intervention.

Research from Nature Portfolio

Recent studies have identified ApoL6 as a lipid-droplet-associated protein whose nutrient-responsive expression governs droplet size and triglyceride content. ApoL6 interacts with perilipin 1 to impede its binding to HSL, thereby inhibiting lipolysis and modulating white adipose mass and systemic insulin sensitivity. In parallel, an intrinsic glucose-sensing pathway has been described whereby fluctuations in intracellular glucose alter Golgi phosphatidylinositol 4-phosphate levels, regulating ubiquitylation and activity of ATGL and thus adjusting lipolysis to nutrient availability. Foundational work has also demonstrated that pharmacological inhibition of ATGL with a small-molecule antagonist reduces adipose lipolysis, prevents ectopic lipid deposition and ameliorates obesity-associated insulin resistance, confirming ATGL as a druggable target.

Lipid Metabolism Regulation in Adipose Tissue publication trend

The graph below shows the total number of articles in lipid metabolism regulation in adipose tissue across all publications each year (not limited to Nature Index journals).

Technical terms

Adipocyte: A specialised cell in adipose tissue responsible for lipid storage and release.

Lipid droplet: A cytosolic organelle composed of a neutral lipid core surrounded by a phospholipid monolayer and associated proteins.

Lipolysis: The enzymatic process of hydrolysing stored triglycerides into glycerol and free fatty acids.

Triacylglycerol (TAG): The primary form of energy storage in adipose tissue, consisting of three fatty acid chains esterified to glycerol.

Adipose triglyceride lipase (ATGL): The rate-limiting enzyme that catalyses the initial step of triglyceride hydrolysis.

Hormone-sensitive lipase (HSL): An enzyme that further hydrolyses diacylglycerol to monoacylglycerol during lipolysis, regulated by phosphorylation.

Perilipin 1 (PLIN1): A lipid-droplet-associated protein that controls lipase access to stored triglycerides in response to hormonal signals.

Lysosomal acid lipase (LIPA): An enzyme within lysosomes that mediates an alternative pathway of intracellular lipid degradation.

Golgi phosphatidylinositol 4-phosphate (PtdIns4P): A lipid signalling molecule that regulates enzyme ubiquitin-ligase assembly and ATGL activity in response to glucose levels.

References

1. ApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis. Nature Communications (2024).
2. Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL. Nature Cell Biology (2024).
3. Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis. Journal of Clinical Investigation (2025).
4. Effect of Crocetin on Basal Lipolysis in 3T3-L1 Adipocytes. Antioxidants (2023).
5. Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nature Communications (2017).
6. Of mice and men: The physiological role of adipose triglyceride lipase (ATGL). Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (2018).
7. Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism*. Journal of Biological Chemistry (2006).