After so many years of experience, I am still often asked one question: What exactly happens to the food I eat? And how does it become fat?
Today, I will explain in detail the metabolic process of lipid breakdown and storage in our bodies.
Our bodies constantly transition between states of energy abundance and scarcity. This metabolic flexibility is performed by two opposing processes: lipogenesis, which is the formation of fat molecules during feeding, and lipolysis, which is the breakdown of fat during fasting.
Let me start with lipolysis, it is the process activated in patients who are fasting or exercising. The body mobilises the stored fat to meet the energy demands. When glucose becomes less available, the pancreas reduces insulin secretion while increasing glucagon release. Simultaneously, the adrenal glands secrete epinephrine and norepinephrine.
The breakdown begins with the enzyme adipose triglyceride lipase, which catalyses the conversion of triglycerides to diacylglycerol, and finally, monoglyceride lipase completes the process by releasing glycerol and free fatty acids. I explain to my patients that these hormonal changes are like unlocking the body’s energy vault. The catecholamines bind to β-adrenergic receptors on fat cells, triggering a signalling cascade that increases cyclic AMP. This messenger activates protein kinase A, which phosphorylates two key proteins: perilipin and hormone-sensitive lipase.
Insulin also serves as a potent inhibitor of lipolysis. Upon binding to its receptor, insulin activates the PI3K-Akt pathway, leading to the activation of phosphodiesterase 3B. PDE3B degradescAMP, reducing PKA activity and thereby decreasing lipolysis.
Lipogenesis is the process by which our bodies synthesise fatty acids and triglycerides for energy storage. This primarily occurs in the liver and adipose tissues. The process begins with acetyl-CoA, which is carboxylated by acetyl-CoA carboxylase to form malonyl-CoA. Fatty acid synthase then catalyses the elongation of the carbon chain, producing palmitate, a 16-carbon saturated fatty acid.
These newly synthesised fatty acids are then esterified with glycerol-3-phosphate to form triglycerides, which are stored in lipid droplets within adipocytes or packaged into very-low-density lipoprotein in the liver for transport to other tissues.
Insulin plays a central role in promoting lipogenesis. It upregulates the expression of lipogenic enzymes like ACC and FAS and activates transcription factors such as sterol regulatory element-binding protein-1c.
The equilibrium between lipolysis and lipogenesis is crucial for maintaining energy homeostasis. Dysregulation can lead to metabolic disorders. Excessive lipogenesis and impaired lipolysis contribute to fat accumulation, insulin resistance, and conditions like non-alcoholic fatty liver disease and type 2 diabetes.
Understanding these pathways provides insight into potential therapeutic targets for treating metabolic diseases. Modulating the activity of key enzymes and signalling pathways could offer avenues for intervention.
