Lipokinler
Özet
Lipokinler, adaptif termojenez ve enerji metabolizmasını düzenleyen lipit türevli hormonlardır. Bu moleküller, özellikle kahverengi ve bej yağ dokusunda enerji tüketimini artırarak obezite ve metabolik bozukluklarla mücadelede önemli terapötik hedefler sunmaktadır. Termojenik lipokinler arasında oleiletanolamin (OEA), prostaglandin E2 (PGE2) ve 12,13-diHOME gibi bileşikler yer alır. OEA, iştahı baskılayarak kilo kaybını teşvik ederken, PGE2 kahverengi yağ dokusu aktivitesini artırır. 12,13-diHOME ise yağ asitlerinin kas ve kahverengi yağ dokusuna alımını düzenler.
Lipokinlerin etkileri, genellikle hücresel enzimler ve reseptörler aracılığıyla gerçekleşir. Örneğin, OEA, GPR119 ve PPAR gibi reseptörleri aktive ederken, PGE2 ve 12,13-diHOME'nin etkileri prostaglandin ve TRPV1 reseptörleri üzerinden gerçekleşir. Bununla birlikte, lipokinlerin hızlı metabolize edilmesi ve biyolojik çeşitlilikleri, terapötik uygulamalarını sınırlayan faktörlerdir.
Bu moleküllerin biyosentez, yapısal özellikler ve yıkım süreçlerinin daha iyi anlaşılması, metabolik bozuklukların tedavisine yönelik yeni yaklaşımlar geliştirilmesini mümkün kılabilir. Lipokinlere yönelik araştırmalar, obezite ve ilişkili hastalıklara karşı umut vadeden çözümler sunmaktadır.
Lipokines are lipid-derived hormones that regulate adaptive thermogenesis and energy metabolism. These molecules play a significant role in combating obesity and metabolic disorders by enhancing energy expenditure, particularly in brown and beige adipose tissues. Thermogenic lipokines include compounds such as oleoylethanolamide (OEA), prostaglandin E2 (PGE2), and 12,13-diHOME. OEA promotes weight loss by suppressing appetite, while PGE2 increases brown adipose tissue activity. 12,13-diHOME, on the other hand, regulates the uptake of fatty acids into muscles and brown adipose tissue.
The effects of lipokines are mediated primarily through cellular enzymes and receptors. For instance, OEA activates receptors such as GPR119 and PPAR, whereas the effects of PGE2 and 12,13-diHOME are mediated through prostaglandin and TRPV1 receptors. However, the rapid metabolism and biological diversity of lipokines pose challenges to their therapeutic applications.
A deeper understanding of the biosynthesis, structural properties, and degradation processes of these molecules could facilitate the development of novel approaches to treat metabolic disorders. Research on lipokines offers promising solutions for addressing obesity and related diseases.
Referanslar
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Lynes MD, Shamsi F, Sustarsic EG, et al. Cold-Activated Lipid Dynamics in Adipose Tissue Highlights a Role for Cardiolipin in Thermogenic Metabolism. Cell Rep. Elsevier; 2018;24(3):781–790. doi: 10.1016/J.CELREP.2018.06.073.
Carpentier AC, Blondin DP, Virtanen KA, et al. Brown Adipose Tissue Energy Metabolism in Humans. Front Endocrinol (Lausanne). Frontiers Media SA; 2018;9. doi: 10.3389/FENDO.2018.00447.
Blondin DP, Labbé SM, Phoenix S, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol. Wiley; 2015;593(3):701–714. doi: 10.1113/JPHYSIOL.2014.283598.
Hanssen MJW, Hoeks J, Brans B, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med. Springer; 2015;21(8):863–865. doi: 10.1038/NM.3891.
LeBlanc J. Mechanisms of adaptation to cold. Int J Sports Med. Thieme; 1992;13(1). doi: 10.1055/S-2007-1024629.
Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev. Cold Spring Harbor Laboratory Press; 2013;27(3):234–250. doi: 10.1101/GAD.211649.112.
Ježek P, Jabůrek M, Porter RK. Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1). Biochim Biophys Acta Bioenerg. Elsevier; 2019;1860(3):259–269. doi: 10.1016/J.BBABIO.2018.11.007.
Kazak L, Chouchani ET, Lu GZ, et al. Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity. Cell Metab. Elsevier; 2017;26(4):660-671.e3. doi: 10.1016/J.CMET.2017.08.009.
Kazak L, Chouchani ET, Jedrychowski MP, et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell. Elsevier; 2015;163(3):643–655. doi: 10.1016/J.CELL.2015.09.035.
Rowland LA, Bal NC, Kozak LP, Periasamy M. Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis, and Loss of Both Systems Compromises Survival of Mice under Cold Stress. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2015;290(19):12282–12289. doi: 10.1074/JBC.M115.637603.
Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. Massachusetts Medical Society; 2009;360(15):1509–1517. doi: 10.1056/NEJMOA0810780.
Braun K, Oeckl J, Westermeier J, et al. Non-adrenergic control of lipolysis and thermogenesis in adipose tissues. J Exp Biol. The Company of Biologists Ltd; 2018;221(1). doi: 10.1242/JEB.165381.
Kong M, Zhang H, Cao X, Mao X, Lu Z. Higher level of Neutrophil-to-Lymphocyte is associated with severe COVID-19. Epidemiol Infect. Cambridge University Press; 2020;148. doi: 10.1017/S0950268820001557.
Cao H, Gerhold K, Mayers JR, et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. Elsevier; 2008;134(6):933–944. doi: 10.1016/J.CELL.2008.07.048.
Fleckenstein-Elsen M, Dinnies D, Jelenik T, et al. Eicosapentaenoic acid and arachidonic acid differentially regulate adipogenesis, acquisition of a brite phenotype and mitochondrial function in primary human adipocytes. Mol Nutr Food Res. Wiley; 2016;60(9):2065–2075. doi: 10.1002/MNFR.201500892.
Long JZ, Svensson KJ, Bateman LA, et al. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria. Cell. Elsevier; 2016;166(2):424–435. doi: 10.1016/J.CELL.2016.05.071.
Gregoriadis G. Drug entrapment in liposomes. FEBS Lett. Wiley; 1973;36(3):292–296. doi: 10.1016/0014-5793(73)80394-1.
Long JZ, Roche AM, Berdan CA, et al. Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception. Proc Natl Acad Sci U S A. National Academy of Sciences; 2018;115(29).E6945. doi: 10.1073/PNAS.1803389115.
Decara JM, Romero-Cuevas M, Rivera P, et al. Elaidyl-sulfamide, an oleoylethanolamide-modelled PPARα agonist, reduces body weight gain and plasma cholesterol in rats. Dis Model Mech. The Company of Biologists Ltd; 2012;5(5):660–670. doi: 10.1242/DMM.009233.
Ogura Y, Parsons WH, Kamat SS, Cravatt BF. A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines. Nat Chem Biol. Springer; 2016;12(9):669–671. doi: 10.1038/NCHEMBIO.2127.
Huggins JP, Smart TS, Langman S, et al. An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain. Wolters Kluwer; 2012;153(9):1837–1846. doi: 10.1016/J.PAIN.2012.04.020.
Egertová M, Simon GM, Cravatt BF, Elphick MR. Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective on N-acylethanolamines as neural signaling molecules. J Comp Neurol. Wiley; 2008;506(4):604–615. doi: 10.1002/CNE.21568.
Koreck A, Pivarcsi A, Dobozy A, Kemény L. The Role of Innate Immunity in the Pathogenesis of Acne. Dermatology. Karger Publishers; 2003;206(2):96–105. doi: 10.1159/000068476.
Suárez J, Rivera P, Arrabal S, et al. Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat. Dis Model Mech. The Company of Biologists Ltd; 2014;7(1):129–141. doi: 10.1242/DMM.013110.
Bayindir I, Babaeikelishomi R, Kocanova S, et al. Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Front Endocrinol (Lausanne). Frontiers Media SA; 2015;6(8). doi: 10.3389/FENDO.2015.00129.
Pisani DF, Ghandour RA, Beranger GE, et al. The ω6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway. Mol Metab. Elsevier; 2014;3(9):834–847. doi: 10.1016/J.MOLMET.2014.09.003.
Amir S, Schiavetto A. Injection of prostaglandin E2 into the anterior hypothalamic preoptic area activates brown adipose tissue thermogenesis in the rat. Brain Res. Elsevier; 1990;528(1):138–142. doi: 10.1016/0006-8993(90)90206-Q.
Chu X, Xu L, Nishimura K, et al. Suppression of adipogenesis program in cultured preadipocytes transfected stably with cyclooxygenase isoforms. Biochim Biophys Acta. Elsevier; 2009;1791(4):273–280. doi: 10.1016/J.BBALIP.2009.01.022.
Kim DH, Puri N, Sodhi K, et al. Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes. J Lipid Res. American Society for Biochemistry and Molecular Biology; 2013;54(3):786–793. doi: 10.1194/JLR.M033894.
Pierre C, Guillebaud F, Airault C, et al. Invalidation of Microsomal Prostaglandin E Synthase-1 (mPGES-1) Reduces Diet-Induced Low-Grade Inflammation and Adiposity. Front Physiol. Frontiers Media SA; 2018;9(1). doi: 10.3389/FPHYS.2018.01358.
Zhang G, Kodani S, Hammock BD. Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer. Prog Lipid Res. Elsevier; 2014;53(1):108–123. doi: 10.1016/J.PLIPRES.2013.11.003.
Edin ML, Hamedani BG, Gruzdev A, et al. Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2018;293(9):3281–3292. doi: 10.1074/JBC.RA117.000298.
Pickens CA, Sordillo LM, Zhang C, Fenton JI. Obesity is positively associated with arachidonic acid-derived 5- and 11-hydroxyeicosatetraenoic acid (HETE). Metabolism. Elsevier; 2017;70(5):177–191. doi: 10.1016/J.METABOL.2017.01.034.
Nieman DC, Shanely RA, Luo B, et al. Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling. Am J Physiol Regul Integr Comp Physiol. American Physiological Society; 2014;307(1). doi: 10.1152/AJPREGU.00092.2014. Cited: PMID: 24760997.
Lynes MD, Leiria LO, Lundh M, et al. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med. Springer; 2017;23(5):631–637. doi: 10.1038/NM.4297. Cited: PMID: 28346411.
Stanford KI, Lynes MD, Takahashi H, et al. 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake. Cell Metab. Elsevier; 2018;27(5):1111-1120.e3. doi: 10.1016/J.CMET.2018.03.020. Cited: PMID: 29719226.
Green DP, Ruparel S, Gao X, et al. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol Pain. Sage Publications; 2016;12(7). doi: 10.1177/1744806916661725. Cited: PMID: 27411353.
Pertwee RG, Howlett AC, Abood ME, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. American Society for Pharmacology and Experimental Therapeutics; 2010;62(4):588–631. doi: 10.1124/PR.110.003004.
Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. Wiley; 2007;152(7):1092–1101. doi: 10.1038/SJ.BJP.0707460.
Rossi F, Punzo F, Umano GR, et al. Role of Cannabinoids in Obesity. Int J Mol Sci. MDPI; 2018;19(9). doi: 10.3390/IJMS19092690.
Gill EW, Paton WDM, Pertwee RG. Preliminary experiments on the chemistry and pharmacology of cannabis. Nature. Springer; 1970;228(5267):134–136. doi: 10.1038/228134A0. Cited: PMID: 5466704.
Pertwee RG, Nash K, Trayhurn P. Evidence that the hypothermic response of mice to delta-9-tetrahydrocannabinol is not mediated by changes in thermogenesis in brown adipose tissue. Can J Physiol Pharmacol. National Research Council of Canada; 1991;69(6):767–770. doi: 10.1139/Y91-114. Cited: PMID: 1655180.
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Lynes MD, Shamsi F, Sustarsic EG, et al. Cold-Activated Lipid Dynamics in Adipose Tissue Highlights a Role for Cardiolipin in Thermogenic Metabolism. Cell Rep. Elsevier; 2018;24(3):781–790. doi: 10.1016/J.CELREP.2018.06.073.
Carpentier AC, Blondin DP, Virtanen KA, et al. Brown Adipose Tissue Energy Metabolism in Humans. Front Endocrinol (Lausanne). Frontiers Media SA; 2018;9. doi: 10.3389/FENDO.2018.00447.
Blondin DP, Labbé SM, Phoenix S, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol. Wiley; 2015;593(3):701–714. doi: 10.1113/JPHYSIOL.2014.283598.
Hanssen MJW, Hoeks J, Brans B, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med. Springer; 2015;21(8):863–865. doi: 10.1038/NM.3891.
LeBlanc J. Mechanisms of adaptation to cold. Int J Sports Med. Thieme; 1992;13(1). doi: 10.1055/S-2007-1024629.
Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev. Cold Spring Harbor Laboratory Press; 2013;27(3):234–250. doi: 10.1101/GAD.211649.112.
Ježek P, Jabůrek M, Porter RK. Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1). Biochim Biophys Acta Bioenerg. Elsevier; 2019;1860(3):259–269. doi: 10.1016/J.BBABIO.2018.11.007.
Kazak L, Chouchani ET, Lu GZ, et al. Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity. Cell Metab. Elsevier; 2017;26(4):660-671.e3. doi: 10.1016/J.CMET.2017.08.009.
Kazak L, Chouchani ET, Jedrychowski MP, et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell. Elsevier; 2015;163(3):643–655. doi: 10.1016/J.CELL.2015.09.035.
Rowland LA, Bal NC, Kozak LP, Periasamy M. Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis, and Loss of Both Systems Compromises Survival of Mice under Cold Stress. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2015;290(19):12282–12289. doi: 10.1074/JBC.M115.637603.
Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. Massachusetts Medical Society; 2009;360(15):1509–1517. doi: 10.1056/NEJMOA0810780.
Braun K, Oeckl J, Westermeier J, et al. Non-adrenergic control of lipolysis and thermogenesis in adipose tissues. J Exp Biol. The Company of Biologists Ltd; 2018;221(1). doi: 10.1242/JEB.165381.
Kong M, Zhang H, Cao X, Mao X, Lu Z. Higher level of Neutrophil-to-Lymphocyte is associated with severe COVID-19. Epidemiol Infect. Cambridge University Press; 2020;148. doi: 10.1017/S0950268820001557.
Cao H, Gerhold K, Mayers JR, et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. Elsevier; 2008;134(6):933–944. doi: 10.1016/J.CELL.2008.07.048.
Fleckenstein-Elsen M, Dinnies D, Jelenik T, et al. Eicosapentaenoic acid and arachidonic acid differentially regulate adipogenesis, acquisition of a brite phenotype and mitochondrial function in primary human adipocytes. Mol Nutr Food Res. Wiley; 2016;60(9):2065–2075. doi: 10.1002/MNFR.201500892.
Long JZ, Svensson KJ, Bateman LA, et al. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria. Cell. Elsevier; 2016;166(2):424–435. doi: 10.1016/J.CELL.2016.05.071.
Gregoriadis G. Drug entrapment in liposomes. FEBS Lett. Wiley; 1973;36(3):292–296. doi: 10.1016/0014-5793(73)80394-1.
Long JZ, Roche AM, Berdan CA, et al. Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception. Proc Natl Acad Sci U S A. National Academy of Sciences; 2018;115(29).E6945. doi: 10.1073/PNAS.1803389115.
Decara JM, Romero-Cuevas M, Rivera P, et al. Elaidyl-sulfamide, an oleoylethanolamide-modelled PPARα agonist, reduces body weight gain and plasma cholesterol in rats. Dis Model Mech. The Company of Biologists Ltd; 2012;5(5):660–670. doi: 10.1242/DMM.009233.
Ogura Y, Parsons WH, Kamat SS, Cravatt BF. A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines. Nat Chem Biol. Springer; 2016;12(9):669–671. doi: 10.1038/NCHEMBIO.2127.
Huggins JP, Smart TS, Langman S, et al. An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain. Wolters Kluwer; 2012;153(9):1837–1846. doi: 10.1016/J.PAIN.2012.04.020.
Egertová M, Simon GM, Cravatt BF, Elphick MR. Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective on N-acylethanolamines as neural signaling molecules. J Comp Neurol. Wiley; 2008;506(4):604–615. doi: 10.1002/CNE.21568.
Koreck A, Pivarcsi A, Dobozy A, Kemény L. The Role of Innate Immunity in the Pathogenesis of Acne. Dermatology. Karger Publishers; 2003;206(2):96–105. doi: 10.1159/000068476.
Suárez J, Rivera P, Arrabal S, et al. Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat. Dis Model Mech. The Company of Biologists Ltd; 2014;7(1):129–141. doi: 10.1242/DMM.013110.
Bayindir I, Babaeikelishomi R, Kocanova S, et al. Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Front Endocrinol (Lausanne). Frontiers Media SA; 2015;6(8). doi: 10.3389/FENDO.2015.00129.
Pisani DF, Ghandour RA, Beranger GE, et al. The ω6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway. Mol Metab. Elsevier; 2014;3(9):834–847. doi: 10.1016/J.MOLMET.2014.09.003.
Amir S, Schiavetto A. Injection of prostaglandin E2 into the anterior hypothalamic preoptic area activates brown adipose tissue thermogenesis in the rat. Brain Res. Elsevier; 1990;528(1):138–142. doi: 10.1016/0006-8993(90)90206-Q.
Chu X, Xu L, Nishimura K, et al. Suppression of adipogenesis program in cultured preadipocytes transfected stably with cyclooxygenase isoforms. Biochim Biophys Acta. Elsevier; 2009;1791(4):273–280. doi: 10.1016/J.BBALIP.2009.01.022.
Kim DH, Puri N, Sodhi K, et al. Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes. J Lipid Res. American Society for Biochemistry and Molecular Biology; 2013;54(3):786–793. doi: 10.1194/JLR.M033894.
Pierre C, Guillebaud F, Airault C, et al. Invalidation of Microsomal Prostaglandin E Synthase-1 (mPGES-1) Reduces Diet-Induced Low-Grade Inflammation and Adiposity. Front Physiol. Frontiers Media SA; 2018;9(1). doi: 10.3389/FPHYS.2018.01358.
Zhang G, Kodani S, Hammock BD. Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer. Prog Lipid Res. Elsevier; 2014;53(1):108–123. doi: 10.1016/J.PLIPRES.2013.11.003.
Edin ML, Hamedani BG, Gruzdev A, et al. Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2018;293(9):3281–3292. doi: 10.1074/JBC.RA117.000298.
Pickens CA, Sordillo LM, Zhang C, Fenton JI. Obesity is positively associated with arachidonic acid-derived 5- and 11-hydroxyeicosatetraenoic acid (HETE). Metabolism. Elsevier; 2017;70(5):177–191. doi: 10.1016/J.METABOL.2017.01.034.
Nieman DC, Shanely RA, Luo B, et al. Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling. Am J Physiol Regul Integr Comp Physiol. American Physiological Society; 2014;307(1). doi: 10.1152/AJPREGU.00092.2014. Cited: PMID: 24760997.
Lynes MD, Leiria LO, Lundh M, et al. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med. Springer; 2017;23(5):631–637. doi: 10.1038/NM.4297. Cited: PMID: 28346411.
Stanford KI, Lynes MD, Takahashi H, et al. 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake. Cell Metab. Elsevier; 2018;27(5):1111-1120.e3. doi: 10.1016/J.CMET.2018.03.020. Cited: PMID: 29719226.
Green DP, Ruparel S, Gao X, et al. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol Pain. Sage Publications; 2016;12(7). doi: 10.1177/1744806916661725. Cited: PMID: 27411353.
Pertwee RG, Howlett AC, Abood ME, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. American Society for Pharmacology and Experimental Therapeutics; 2010;62(4):588–631. doi: 10.1124/PR.110.003004.
Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. Wiley; 2007;152(7):1092–1101. doi: 10.1038/SJ.BJP.0707460.
Rossi F, Punzo F, Umano GR, et al. Role of Cannabinoids in Obesity. Int J Mol Sci. MDPI; 2018;19(9). doi: 10.3390/IJMS19092690.
Gill EW, Paton WDM, Pertwee RG. Preliminary experiments on the chemistry and pharmacology of cannabis. Nature. Springer; 1970;228(5267):134–136. doi: 10.1038/228134A0. Cited: PMID: 5466704.
Pertwee RG, Nash K, Trayhurn P. Evidence that the hypothermic response of mice to delta-9-tetrahydrocannabinol is not mediated by changes in thermogenesis in brown adipose tissue. Can J Physiol Pharmacol. National Research Council of Canada; 1991;69(6):767–770. doi: 10.1139/Y91-114. Cited: PMID: 1655180.
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Sayfalar
81-92
Gelecek
14 Ocak 2025
Telif Hakkı (c) 2025 Akademisyen Yayınevi Kitap DOI Portalı
