Journal September 25, 2026 5 min read

How does lipolysis work?

Lipolysis is the enzymatic hydrolysis of stored triglycerides into free fatty acids and glycerol. This page covers the mechanism, the enzyme families involved, and what cell, animal and human studies have reported.

peptides-pro Editorial

Lipolysis is the enzymatic hydrolysis of triacylglycerol stored in lipid droplets into free fatty acids and glycerol, releasing fatty acids for oxidation or export. It is not a single reaction but a sequential, multi-enzyme process, and the rate-limiting step in most cells is catalysed by hormone-sensitive lipase (HSL), an enzyme that mobilises fat from adipose tissue. HSL is the enzyme measured as a circulating marker of lipolytic activity in human training studies [7].

The work described on this page centres on the AMP-activated protein kinase (AMPK) signalling axis and its downstream transcriptional and autophagic effectors, together with the G-protein-coupled receptor and sympathetic signalling inputs that feed into it.

Research Studies

Sulforaphane and AMPK-centred lipid metabolism in cell and animal models

Sulforaphane (SFN) is an isothiocyanate produced from glucoraphanin in cruciferous vegetables. In cell and animal models, SFN treatment was associated with ACC phosphorylation, inhibition of mTORC1-SREBP signalling, CPT-1-related fatty acid oxidation, PGC-1α/PPAR-α transcriptional regulation, and ULK1-mediated lipophagy. The same review notes that most studies measured AMPK phosphorylation without pharmacological or genetic confirmation of AMPK dependence, so pathway association should be distinguished from demonstrated requirement [1].

Hepatic Neu1 deficiency and GCGR desialylation in old mice

Neuraminidase 1 (Neu1) removes sialic acid from glycoproteins and glycolipids and influences hepatic glycolipid metabolism. Liver-specific Neu1 knockout mice were constructed to test whether Neu1 acts on hepatic gluconeogenesis through desialylation of the glucagon receptor (GCGR), a pathway linked to cAMP-PKA signalling and inflammatory response. This work is animal-only [2].

Ethanol exposure and ghrelin secretion in vitro

Ghrelin is a stomach-derived orexigenic peptide that rises during fasting. Chronic alcohol consumption elevates circulating ghrelin, which promotes adipose lipolysis and inhibits insulin secretion. The cited study investigated how ethanol modulates ghrelin production and disrupts nutrient sensing in ghrelin-secreting cells, using in vitro mechanistic approaches [3].

Erythropoietin and lipolysis in adipose tissue, skeletal muscle and liver

Erythropoietin (EPO) is the principal regulator of erythrocyte production. Beyond haematopoiesis, EPO influences glucose and fat metabolism in adipose tissue, skeletal muscle and the liver. In white adipose tissue, brown adipose tissue and skeletal muscle, EPO enhances lipolysis while inhibiting lipogenic gene expression [5].

Combined training and serum HSL in overweight and obese men

A randomised controlled trial assigned 36 overweight and obese men to upper body combined training, lower body combined training, or a non-exercising control group. The intervention was 10 weeks of combined resistance and aerobic training three times per week, with serum myostatin (MSTN) and HSL measured as outcomes. HSL is described in that trial as a key enzyme in lipolysis and fat mobilisation [7].

Group	Intervention	Duration	Measured outcomes
Upper body combined training	Resistance plus aerobic, 3×/week	10 weeks	Serum MSTN, serum HSL
Lower body combined training	Resistance plus aerobic, 3×/week	10 weeks	Serum MSTN, serum HSL
Non-exercising control	None	10 weeks	Serum MSTN, serum HSL

hCG and IGF-I measurement in dried blood spots

Human chorionic gonadotropin (hCG) and insulin-like growth factor I (IGF-I) are both on the WADA list of banned molecules. Male athletes may use pharmaceutical hCG to stimulate testosterone production before competition, and IGF-I to stimulate muscle protein synthesis, promote glycogen storage and improve lipolysis. The cited technical note describes a UHPLC-MS/MS method for analysing both hormones from dried blood spots as a doping-control strategy [4].

Alpha ketoglutarate and the surgical stress response

Coronary artery bypass grafting (CABG) is performed in approximately 400,000 patients in the United States each year and invokes a large surgical stress response, with systemic epinephrine rising 33-fold and norepinephrine rising 3-fold. The AEGIS trial addresses geroprotection in this surgical context, where catecholamine surges of this magnitude are the canonical upstream drivers of adipocyte lipolysis [6].

Diet, hepatic transcriptomics and lipidomics in pre-diabetes

Non-alcoholic fatty liver disease (NAFLD) affects 25% to 30% of the global population and is defined as excessive lipid accumulation within hepatocytes without significant alcohol consumption or other chronic liver disease. The cited trial examines diet impact on hepatic transcriptomics and lipidomics in pre-diabetes, a setting in which hepatic lipid handling and adipose lipolytic flux are coupled [8].

Depot-specific differences in human adipose tissue

Paired visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) samples were collected from 22 patients with obesity undergoing elective Roux-en-Y surgery, in a study of depot-specific functional differences and the factors limiting fat cell expandability. This is human tissue work and is reported here as supporting context rather than as a section topic [11].

Central lactate, FGF21 and exercise-induced fat mobilisation

Fibroblast growth factor 21 (FGF21) regulates lipid metabolism. In male Wistar rats, central lactate uptake during exercise was examined as a contributor to hypothalamic FGF21 induction and sympathetic-driven systemic lipolysis. This finding is animal-only [12].

Canagliflozin and adipocyte-intrinsic lipid mobilisation

Canagliflozin (CANA) shows anti-obesity effects in clinical practice, but its direct adipocyte-intrinsic functions are less well understood. In 3T3-L1 preadipocytes, CANA promoted differentiation, with the reported dual action coupling an AMPK/autophagy-dependent pro-adipogenic effect to enhanced lipid mobilisation and thermogenesis. This is in vitro work [9].

Omentin-1 and in vitro porcine oocyte maturation

Omentin-1 enhanced in vitro oocyte maturation by increasing the percentage of oocytes in metaphase II, progesterone levels, mitochondrial function and lipolysis, acting via ERK1/2 and PRKAA1, with no effect on preimplantation embryo development. This is an in vitro porcine model [10].

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