In the body, stores of fat are referred to as
adipose tissue. In these areas, intracellular triglycerides are stored in cytoplasmic
lipid droplets. When
lipase enzymes are phosphorylated, they can access lipid droplets and through multiple steps of hydrolysis, breakdown triglycerides into fatty acids and glycerol. Each step of hydrolysis leads to the removal of one fatty acid. The first step and the rate-limiting step of lipolysis is carried out by
adipose triglyceride lipase (ATGL). This enzyme catalyzes the hydrolysis of
triacylglycerol to
diacylglycerol. Subsequently,
hormone-sensitive lipase (HSL) catalyzes the hydrolysis of diacylglycerol to
monoacylglycerol and
monoacylglycerol lipase (MGL) catalyzes the hydrolysis of monoacylglycerol to
glycerol.[4]
Perilipin 1A is a key protein regulator of lipolysis in adipose tissue. This lipid droplet-associated protein, when deactivated, will prevent the interaction of lipases with triglycerides in the lipid droplet and grasp the ATGL co-activator, comparative gene identification 58 (CGI-58) (a.k.a.
ABHD5). When perilipin 1A is phosphorylated by PKA, it releases CGI-58 and it expedites the docking of phosphorylated lipases to the lipid droplet.[5] CGI-58 can be further phosphorylated by PKA to assist in its dispersal to the cytoplasm. In the cytoplasm, CGI-58 can co-activate ATGL.[6] ATGL activity is also impacted by the negative regulator of lipolysis, G0/G1 switch gene 2 (G0S2). When expressed, G0S2 acts as a competitive inhibitor in the binding of CGI-58.[7] Fat-specific protein 27 (FSP-27) (a.k.a. CIDEC) is also a negative regulator of lipolysis. FSP-27 expression is negatively correlated with ATGL mRNA levels.[8]
Regulation
Lipolysis can be regulated through
cAMP's binding and activation of
protein kinase A (PKA). PKA can phosphorylate lipases, perilipin 1A, and CGI-58 to increase the rate of lipolysis.
Catecholamines bind to
7TM receptors (G protein-coupled receptors) on the adipocyte cell membrane, which activate
adenylate cyclase. This results in increased production of cAMP, which activates PKA and leads to an increased rate of lipolysis. Despite glucagon's lipolytic activity (which stimulates PKA as well)
in vitro, the role of glucagon in lipolysis
in vivo is disputed.[9]
Insulin counter-regulates this increase in lipolysis when it binds to insulin receptors on the adipocyte cell membrane. Insulin receptors activate insulin-like receptor substrates. These substrates activate
phosphoinositide 3-kinases (PI-3K) which then phosphorylate
protein kinase B (PKB) (a.k.a. Akt). PKB subsequently phosphorylates
phosphodiesterase 3B (PD3B), which then converts the cAMP produced by adenylate cyclase into 5'AMP. The resulting insulin induced reduction in cAMP levels decreases the lipolysis rate.[10]
Triglycerides are transported through the blood to appropriate tissues (
adipose,
muscle, etc.) by
lipoproteins such as Very-Low-Density-Lipoproteins (
VLDL). Triglycerides present on the VLDL undergo lipolysis by the cellular lipases of target tissues, which yields
glycerol and free
fatty acids. Free fatty acids released into the blood are then available for cellular uptake.[13][self-published source?] Free fatty acids not immediately taken up by cells may bind to
albumin for transport to surrounding tissues that require energy. Serum albumin is the major carrier of free fatty acids in the blood.[14]
While lipolysis is triglyceride
hydrolysis (the process by which triglycerides are broken down),
esterification is the process by which triglycerides are formed. Esterification and lipolysis are, in essence, reversals of one another.[16]
Medical procedures
Physical lipolysis involves destruction of fat cells containing the fat droplets and can be used as part of cosmetic body contouring procedures. Currently there are four main non-invasive body contouring techniques in
aesthetic medicine for reducing localized subcutaneous
adipose tissue in addition to the standard minimally invasive liposuction: low-level laser therapy (LLLT),
cryolipolysis,
radio frequency (RF) and high-intensity focused ultrasound (HIFU).[17][18] However, they are less effective with shorter lasting benefits and can remove significantly smaller amounts of fat compared to traditional surgical liposuction or lipectomy. However, future drug developments can be potentially combined with smaller procedures to augment the result.[citation needed]
^Baldwin, Kenneth David Sutherland; Brooks, George H.; Fahey, Thomas D. (2005). Exercise physiology: human bioenergetics and its applications. New York: McGraw-Hill.
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^Kennedy, J.; Verne, S.; Griffith, R.; Falto-Aizpurua, L.; Nouri, K. (2015). "Non-invasive subcutaneous fat reduction: A review". Journal of the European Academy of Dermatology and Venereology. 29 (9): 1679–88.
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^Mulholland, R. Stephen; Paul, Malcolm D.; Chalfoun, Charbel (2011). "Noninvasive Body Contouring with Radiofrequency, Ultrasound, Cryolipolysis, and Low-Level Laser Therapy". Clinics in Plastic Surgery. 38 (3): 503–20, vii–iii.
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