Figure 3. An overview of lipolysis and lipid oxidation in healthy conditions.

(A) Lipolysis is the hydrolytic conversion of triglycerides (TG) into glycerol and free fatty acids (FFAs) and is most abundant in white and brown adipose tissue. This process is tightly regulated by glucagon, (nor)epinephrine, and other hormones, but also by pro‐inflammatory cytokines. Hydrolysis of the ester bonds between long‐chain fatty acids and the glycerol backbone is executed by lipases. Up to now, three enzymes have been implicated in performing the complete hydrolysis of TG into FFAs and glycerol: adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), and monoglyceride lipase (MGL). The FFAs are released into the blood stream and can be taken up by peripheral organs to produce energy via mitochondrial β‐oxidation. (B) Fatty acid β‐oxidation is a multistep process breaking down fatty acids in the mitochondria of the cell to produce acetyl‐CoA, which can be used by the tricarboxylic acid (TCA) cycle to produce ATP. In brief, FFAs are transported across the cell membrane by members of the FATP transporter family. Once inside the cytosol, the FFA is coupled to coenzyme A (CoA) by acyl‐CoA synthetase (ACS) and shuttled across the inner mitochondrial membrane by carnitine palmitoyltransferase II (CPT2) and the carnitine acyltransferase (CAT) after being coupled to carnitine by carnitine palmitoyltransferase I (CPT1). In the mitochondrial matrix, β‐oxidation is conducted by cleaving two carbon molecules in every oxidation cycle to form acetyl‐CoA. The cycle is repeated until the complete fatty acid has been reduced to acetyl‐CoA, which is subsequently enters the TCA cycle.