Lipolysis // is the breakdown of lipids and involves hydrolysis of triglycerides into glycerol and free fatty acids. Predominantly occurring in adipose tissue, lipolysis is used to mobilize stored energy during fasting or exercise. Lipolysis is directly induced in adipocytes by glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.
In adipose tissue, intracellular triglycerides are stored in cytoplasmic lipid droplets. When lipases are phosphorylated, they 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. 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. 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. 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. 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.
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. 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 converts cAMP, produced by adenylate cyclase, into 5'AMP. Due to the reduced levels of cAMP, insulin decreases the rate of lipolysis. Insulin has additional actions in the mediobasal hypothalamus. It has been shown to suppress lipolysis due to lower sympathetic nervous outflow to white adipose tissue. The regulation of this process involves interactions between insulin receptors and gangliosides present in the neuronal cell membrane.
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. 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. The glycerol also enters the bloodstream and is absorbed by the liver or kidney where it is converted to glycerol 3-phosphate by the enzyme glycerol kinase. Hepatic glycerol 3-phosphate is converted mostly into dihydroxyacetonephosphate (DHAP) and then glyceraldehyde 3-phosphate (GA3P) to rejoin the glycolysis and gluconeogenesis pathway.
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.
Currently there are four main non-invasive body contouring techniques growing in aesthetic medicine for reducing localized subcutaneous adipose tissue: low-level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high-intensity focused ultrasound (HIFU).
- Duncan, Robin E.; Ahmadian, Maryam; Jaworski, Kathy; Sarkadi-Nagy, Eszter; Sul, Hei Sook (August 2007). "Regulation of Lipolysis in Adipocytes". Annual Review of Nutrition. 27 (1): 79–101. doi:10.1146/annurev.nutr.27.061406.093734.
- Nielsen, TS; Jessen, N; Jørgensen, JO; Møller, N; Lund, S (June 2014). "Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease". Journal of molecular endocrinology. 52 (3): R199–222. doi:10.1530/JME-13-0277. PMID 24577718.
- Frühbeck, G; Méndez-Giménez, L; Fernández-Formoso, JA; Fernández, S; Rodríguez, A (June 2014). "Regulation of adipocyte lipolysis". Nutrition research reviews. 27 (1): 63–93. doi:10.1017/S095442241400002X. PMID 24872083.
- Itabe, H; Yamaguchi, T; Nimura, S; Sasabe, N (28 April 2017). "Perilipins: a diversity of intracellular lipid droplet proteins". Lipids in health and disease. 16 (1): 83. doi:10.1186/s12944-017-0473-y. PMID 28454542.
- Sahu-Osen, A; Montero-Moran, G; Schittmayer, M; Fritz, K; Dinh, A; Chang, YF; McMahon, D; Boeszoermenyi, A; Cornaciu, I; Russell, D; Oberer, M; Carman, GM; Birner-Gruenberger, R; Brasaemle, DL (January 2015). "CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization". Journal of Lipid Research. 56 (1): 109–21. doi:10.1194/jlr.M055004. PMID 25421061.
- Cornaciu, I; Boeszoermenyi, A; Lindermuth, H; Nagy, HM; Cerk, IK; Ebner, C; Salzburger, B; Gruber, A; Schweiger, M; Zechner, R; Lass, A; Zimmermann, R; Oberer, M (2011). "The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively". PLOS One. 6 (10): e26349. doi:10.1371/journal.pone.0026349. PMID 22039468.
- Singh, M; Kaur, R; Lee, MJ; Pickering, RT; Sharma, VM; Puri, V; Kandror, KV (23 May 2014). "Fat-specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of transcription factor Egr1 on transcription of adipose triglyceride lipase". The Journal of Biological Chemistry. 289 (21): 14481–7. doi:10.1074/jbc.C114.563080. PMID 24742676.
- Jocken, JW; Blaak, EE (23 May 2008). "Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity". Physiology & Behavior. 94 (2): 219–30. doi:10.1016/j.physbeh.2008.01.002. PMID 18262211.
- Scherer T.; O'Hare J.; Diggs-Andrews K.; Schweizer M.; Check B.; Lindner C.; et al. (February 1, 2011). "Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis". Cell Metabolism. 13 (2). doi:10.1016/j.cmet.2011.01.008.
- Herzer, Silke; Meldner, Sascha; Gröne, Hermann-Josef; Nordström, Viola (2015-10-01). "Fasting-Induced Lipolysis and Hypothalamic Insulin Signaling Are Regulated by Neuronal Glucosylceramide Synthase" (PDF). Diabetes. 64 (10): 3363–3376. doi: . ISSN 0012-1797. PMID 26038579.
- King, Michael W. "Oxidation of Fatty Acids". Retrieved 9 April 2012.[self-published source?]
- Tom Brody, Nutritional Biochemistry, (Academic Press, 2nd edition 1999), 215-216. ISBN 0121348369
- Baldwin, Kenneth David Sutherland; Brooks, George H.; Fahey, Thomas D. (2005). Exercise physiology: human bioenergetics and its applications. New York: McGraw-Hill. ISBN 0-07-255642-0.[page needed]
- 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: 1679–88. doi:10.1111/jdv.12994. PMID 25664493.
- 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. doi:10.1016/j.cps.2011.05.002. PMID 21824546.