Hepatokine: Difference between revisions
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== Function == |
== Function == |
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[[File:Hepatic production of secreted factors controls nutrient and energy homeostasis.jpg|thumb|'''Hepatic production of secreted factors controls nutrient and energy homeostasis''']] |
[[File:Hepatic production of secreted factors controls nutrient and energy homeostasis.jpg|thumb|'''Hepatic production of secreted factors controls nutrient and energy homeostasis''']] |
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Hepatokines are hormone-like proteins secreted by hepatocytes, and many have been associated with extra-hepatic metabolic regulation. Through processes like autocrinem, paracrinem, and endocrine signaling, hepatokines can influence metabolic processes.<ref name = "Meex_2017" /> It has been stated that, "hepatocytes secrete more than 560 types of hepatokines, many of which regulate metabolic and inflammatory diseases in the liver or at distant organs through circulation delivery."<ref name = "Jensen-Cody_2021">{{cite journal | vauthors = Jensen-Cody SO, Potthoff MJ | title = Hepatokines and metabolism: Deciphering communication from the liver | journal = Molecular Metabolism | volume = 44 | pages = 101138 | date = February 2021 | pmid = 33285302 | doi = 10.1016/j.molmet.2020.101138 }}</ref> Hepatocytes can secrete multiple hepatokines into the blood. In particular, these hepatokines, similar to hypothalamic hormones and insulin, are structurally polypeptides, and proteins and are transcribed and expressed by specific genes. |
Hepatokines are hormone-like proteins secreted by hepatocytes, and many have been associated with extra-hepatic metabolic regulation. Through processes like autocrinem, paracrinem, and endocrine signaling, hepatokines can influence metabolic processes.<ref name = "Meex_2017" /> It has been stated that, "hepatocytes secrete more than 560 types of hepatokines, many of which regulate metabolic and inflammatory diseases in the liver or at distant organs through circulation delivery."<ref name = "Jensen-Cody_2021">{{cite journal | vauthors = Jensen-Cody SO, Potthoff MJ | title = Hepatokines and metabolism: Deciphering communication from the liver | journal = Molecular Metabolism | volume = 44 | pages = 101138 | date = February 2021 | pmid = 33285302 | doi = 10.1016/j.molmet.2020.101138 | pmc = 7788242 }}</ref> Hepatocytes can secrete multiple hepatokines into the blood. In particular, these hepatokines, similar to hypothalamic hormones and insulin, are structurally polypeptides, and proteins and are transcribed and expressed by specific genes. |
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The liver may emit hepatokines to influence energy homeostasis and inflammation under pressure on the metabolism like long-term starvation or over-nutrition. If the liver is unable to fulfill this process, the corresponding disease develops like fatty liver disease from, "impaired hepatic insulin-sensitizing substance production."<ref name = "Jensen-Cody_2021" /> Hepatokines signal energy status and help regulate nutrient availability to multiple peripheral tissues and the central nervous system (CNS).<ref name = "Jensen-Cody_2021" /> Hepatokines have been described to be involved in the regulation of energy and nutrient metabolism by acting directly on the liver or on distal target tissues. These proteins regulate glucose and lipid metabolism in the liver but also in the skeletal muscle or the adipose tissue. It is now clear that a single session of exercise is accompanied by the production of liver-secreted proteins. Hepatokines can also mediate the beneficial effects of chronic exercise or, at least, represent biomarkers of training-induced metabolic improvements.<ref>{{cite journal | vauthors = Ennequin G, Sirvent P, Whitham M | title = Role of exercise-induced hepatokines in metabolic disorders | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 317 | issue = 1 | pages = |
The liver may emit hepatokines to influence energy homeostasis and inflammation under pressure on the metabolism like long-term starvation or over-nutrition. If the liver is unable to fulfill this process, the corresponding disease develops like fatty liver disease from, "impaired hepatic insulin-sensitizing substance production."<ref name = "Jensen-Cody_2021" /> Hepatokines signal energy status and help regulate nutrient availability to multiple peripheral tissues and the central nervous system (CNS).<ref name = "Jensen-Cody_2021" /> Hepatokines have been described to be involved in the regulation of energy and nutrient metabolism by acting directly on the liver or on distal target tissues. These proteins regulate glucose and lipid metabolism in the liver but also in the skeletal muscle or the adipose tissue. It is now clear that a single session of exercise is accompanied by the production of liver-secreted proteins. Hepatokines can also mediate the beneficial effects of chronic exercise or, at least, represent biomarkers of training-induced metabolic improvements.<ref>{{cite journal | vauthors = Ennequin G, Sirvent P, Whitham M | title = Role of exercise-induced hepatokines in metabolic disorders | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 317 | issue = 1 | pages = E11–E24 | date = July 2019 | pmid = 30964704 | doi = 10.1152/ajpendo.00433.2018 | s2cid = 106409704 | url = http://pure-oai.bham.ac.uk/ws/files/68944742/119967_2_merged_1553692814.pdf }}</ref> Hepatokines directly affect the progression of atherosclerosis by modulating endothelial dysfunction and infiltration of inflammatory cells into vessel walls.<ref>{{cite journal | vauthors = Yoo HJ, Choi KM | title = Hepatokines as a Link between Obesity and Cardiovascular Diseases | journal = Diabetes & Metabolism Journal | volume = 39 | issue = 1 | pages = 10–15 | date = February 2015 | pmid = 25729707 | doi = 10.4093/dmj.2015.39.1.10 | pmc = 4342531 }}</ref> |
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== Types == |
== Types == |
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[[File:Feutin_A.jpg|thumb|'''(A)''' Fetuin-A structure. '''(B)''' Fetuin-A biosynthesis.]] |
[[File:Feutin_A.jpg|thumb|'''(A)''' Fetuin-A structure. '''(B)''' Fetuin-A biosynthesis.]] |
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* [[Fetuin-A]] was the first hepatokine to be described and correlated with increased inflammation and insulin resistance.<ref name = "Iroz_2015">{{cite journal | vauthors = Iroz A, Couty JP, Postic C | title = Hepatokines: unlocking the multi-organ network in metabolic diseases | journal = Diabetologia | volume = 58 | issue = 8 | pages = 1699–1703 | date = August 2015 | pmid = 26032022 | doi = 10.1007/s00125-015-3634-4 }}</ref> |
* [[Fetuin-A]] was the first hepatokine to be described and correlated with increased inflammation and insulin resistance.<ref name = "Iroz_2015">{{cite journal | vauthors = Iroz A, Couty JP, Postic C | title = Hepatokines: unlocking the multi-organ network in metabolic diseases | journal = Diabetologia | volume = 58 | issue = 8 | pages = 1699–1703 | date = August 2015 | pmid = 26032022 | doi = 10.1007/s00125-015-3634-4 | s2cid = 7141228 }}</ref> |
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* [[Fetuin-B]] significantly increases hepatic steatosis and mediates impaired insulin action and glucose intolerance.<ref name="Yakout_2023">{{cite journal | vauthors = Yakout SM, Hussein S, Al-Attas OS, Hussain SD, Saadawy GM, Al-Daghri NM | title = Hepatokines fetuin A and fetuin B status in women with/without gestational diabetes mellitus | journal = American Journal of Translational Research | volume = 15 | issue = 2 | pages = 1291–1299 | date = 2023 | pmid = 36915725 | pmc = 10006815 | doi = | url = }}</ref> |
* [[Fetuin-B]] significantly increases hepatic steatosis and mediates impaired insulin action and glucose intolerance.<ref name="Yakout_2023">{{cite journal | vauthors = Yakout SM, Hussein S, Al-Attas OS, Hussain SD, Saadawy GM, Al-Daghri NM | title = Hepatokines fetuin A and fetuin B status in women with/without gestational diabetes mellitus | journal = American Journal of Translational Research | volume = 15 | issue = 2 | pages = 1291–1299 | date = 2023 | pmid = 36915725 | pmc = 10006815 | doi = | url = }}</ref> |
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* [[ANGPTL8]]/betatrophin, initially proposed for its action on beta cell proliferation, although this effect has recently been brought into question.<ref name = "Iroz_2015" /> |
* [[ANGPTL8]]/betatrophin, initially proposed for its action on beta cell proliferation, although this effect has recently been brought into question.<ref name = "Iroz_2015" /> |
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* [[FGF21|FGF-21]] an insulin-sensitising hormone that is an appealing drug target because of its beneficial metabolic actions.<ref name = "Iroz_2015" /> |
* [[FGF21|FGF-21]] an insulin-sensitising hormone that is an appealing drug target because of its beneficial metabolic actions.<ref name = "Iroz_2015" /> |
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* [[Adropin]] is linked to macronutrient intake.<ref name = "Smati_2020">{{cite journal | vauthors = Smati S, Régnier M, Fougeray T, Polizzi A, Fougerat A, Lasserre F, Lukowicz C, Tramunt B, Guillaume M, Burnol AF, Postic C, Wahli W, Montagner A, Gourdy P, Guillou H | display-authors = 6 | title = Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes | journal = Diabetes & Metabolism | volume = 46 | issue = 2 | pages = 129–136 | date = April 2020 | pmid = 31163275 | doi = 10.1016/j.diabet.2019.05.005 }}</ref> |
* [[Adropin]] is linked to macronutrient intake.<ref name = "Smati_2020">{{cite journal | vauthors = Smati S, Régnier M, Fougeray T, Polizzi A, Fougerat A, Lasserre F, Lukowicz C, Tramunt B, Guillaume M, Burnol AF, Postic C, Wahli W, Montagner A, Gourdy P, Guillou H | display-authors = 6 | title = Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes | journal = Diabetes & Metabolism | volume = 46 | issue = 2 | pages = 129–136 | date = April 2020 | pmid = 31163275 | doi = 10.1016/j.diabet.2019.05.005 | s2cid = 174810284 | url = https://hal.archives-ouvertes.fr/hal-02402566/file/hepatokines%20diabetes%20and%20metabolism%20final.pdf }}</ref> |
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* [[ANGPTL4]] can inhibit lipoprotein lipase and activate cAMP-stimulated lipolysis in adipocytes.<ref>{{cite journal | vauthors = Zhang Y, Zhu Z, Sun L, Yin W, Liang Y, Chen H, Bi Y, Zhai W, Yin Y, Zhang W | title = Hepatic G Protein-Coupled Receptor 180 Deficiency Ameliorates High Fat Diet-Induced Lipid Accumulation via the Gi-PKA-SREBP Pathway | journal = Nutrients | date = April 2023 | volume = 15 | issue =8 | pages = 1838 | doi = 10.3390/nu15081838 }}</ref> |
* [[ANGPTL4]] can inhibit lipoprotein lipase and activate cAMP-stimulated lipolysis in adipocytes.<ref>{{cite journal | vauthors = Zhang Y, Zhu Z, Sun L, Yin W, Liang Y, Chen H, Bi Y, Zhai W, Yin Y, Zhang W | title = Hepatic G Protein-Coupled Receptor 180 Deficiency Ameliorates High Fat Diet-Induced Lipid Accumulation via the Gi-PKA-SREBP Pathway | journal = Nutrients | date = April 2023 | volume = 15 | issue =8 | pages = 1838 | doi = 10.3390/nu15081838 | doi-access = free }}</ref> |
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== Clinical signifance == |
== Clinical signifance == |
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Hepatokines can serve as biomarkers and are potential therapeutic targets for metabolic diseases. The liver through execretion of hepatokines regulates the whole bodies metabolism in response to stress signals.<ref name = "Iroz_2015" /> |
Hepatokines can serve as biomarkers and are potential therapeutic targets for metabolic diseases. The liver through execretion of hepatokines regulates the whole bodies metabolism in response to stress signals.<ref name = "Iroz_2015" /> |
||
Secreted hepatokines in response to exercise induce favorable metabolic changes in fat, blood vessles, and skeletal muscle that can reduce metabolic diseases.<ref>{{cite journal | vauthors = Seo DY, Park SH, Marquez J, Kwak HB, Kim TN, Bae JH, Koh JH, Han J | display-authors = 6 | title = Hepatokines as a Molecular Transducer of Exercise | journal = Journal of Clinical Medicine | volume = 10 | issue = 3 | date = January 2021 | pmid = 33498410 | doi = 10.3390/jcm10030385 }}</ref> |
Secreted hepatokines in response to exercise induce favorable metabolic changes in fat, blood vessles, and skeletal muscle that can reduce metabolic diseases.<ref>{{cite journal | vauthors = Seo DY, Park SH, Marquez J, Kwak HB, Kim TN, Bae JH, Koh JH, Han J | display-authors = 6 | title = Hepatokines as a Molecular Transducer of Exercise | journal = Journal of Clinical Medicine | volume = 10 | issue = 3 | date = January 2021 | page = 385 | pmid = 33498410 | doi = 10.3390/jcm10030385 | pmc = 7864203 | doi-access = free }}</ref> |
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Although substantial progress has been made in understanding disease-controlled production of hepatokines, there is still so much to discover. There is so much room for discovery. For example, "little is known about the inductive mechanism of transcriptional reprogramming, protein translation, modification, and secretion of hepatokines, particularly through the ER and Golgi, and more.<ref name = "Wang_2021" /> The identification and functional characterization of hepatokines may provide significant insights that could help in better understanding of MetS pathogenesis.<ref>{{cite journal | vauthors = Esfahani M, Baranchi M, Goodarzi MT | title = The implication of hepatokines in metabolic syndrome | journal = Diabetes & Metabolic Syndrome | volume = 13 | issue = 4 | pages = 2477–2480 | pmid = 31405664 | doi = 10.1016/j.dsx.2019.06.027 }}</ref> |
Although substantial progress has been made in understanding disease-controlled production of hepatokines, there is still so much to discover. There is so much room for discovery. For example, "little is known about the inductive mechanism of transcriptional reprogramming, protein translation, modification, and secretion of hepatokines, particularly through the ER and Golgi, and more.<ref name = "Wang_2021" /> The identification and functional characterization of hepatokines may provide significant insights that could help in better understanding of MetS pathogenesis.<ref>{{cite journal | vauthors = Esfahani M, Baranchi M, Goodarzi MT | title = The implication of hepatokines in metabolic syndrome | journal = Diabetes & Metabolic Syndrome | year = 2019 | volume = 13 | issue = 4 | pages = 2477–2480 | pmid = 31405664 | doi = 10.1016/j.dsx.2019.06.027 | s2cid = 198296158 }}</ref> |
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=== Non-alcoholic fatty liver disease === |
=== Non-alcoholic fatty liver disease === |
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Hepatokines, sometimes referred to as hepatocytes-derived cytokines<ref>{{cite journal | vauthors = Lu Y, Zheng MH, Wang H | title = Are hepatocytes endocrine cells? | journal = Metabolism and Target Organ Damage. | date = March 2023 | volume = 3 | issue = 1 | page = 3 | doi = 10.20517/mtod.2023.11 }}</ref> have been shown to relate to non-alcoholic fatty liver disease. "Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease.<ref>{{cite journal | vauthors = Kim TH, Hong DG, Yang YM | title = Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism | journal = Biomedicines | volume = 9 | issue = 12 | date = December 2021 | pmid = 34944728 | doi = 10.3390/biomedicines9121903 }}</ref> Not only are they involved with metabolic diseseases but they are also linked to diseases of other organs, such as the heart, muscle, bone, and eyes.<ref name = "Wang_2021">{{cite journal | vauthors = Wang F, So KF, Xiao J, Wang H | title = Organ-organ communication: The liver's perspective | date = January 2021 | journal = Theranostics | volume = 11 | issue = 7 | pages = 3317–3330 | pmid = 33537089 | doi = 10.7150/thno.55795 }}</ref> |
Hepatokines, sometimes referred to as hepatocytes-derived cytokines<ref>{{cite journal | vauthors = Lu Y, Zheng MH, Wang H | title = Are hepatocytes endocrine cells? | journal = Metabolism and Target Organ Damage. | date = March 2023 | volume = 3 | issue = 1 | page = 3 | doi = 10.20517/mtod.2023.11 | s2cid = 257890679 }}</ref> have been shown to relate to non-alcoholic fatty liver disease. "Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease.<ref>{{cite journal | vauthors = Kim TH, Hong DG, Yang YM | title = Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism | journal = Biomedicines | volume = 9 | issue = 12 | date = December 2021 | page = 1903 | pmid = 34944728 | doi = 10.3390/biomedicines9121903 | pmc = 8698516 | doi-access = free }}</ref> Not only are they involved with metabolic diseseases but they are also linked to diseases of other organs, such as the heart, muscle, bone, and eyes.<ref name = "Wang_2021">{{cite journal | vauthors = Wang F, So KF, Xiao J, Wang H | title = Organ-organ communication: The liver's perspective | date = January 2021 | journal = Theranostics | volume = 11 | issue = 7 | pages = 3317–3330 | pmid = 33537089 | doi = 10.7150/thno.55795 | pmc = 7847667 }}</ref> |
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== See also == |
== See also == |
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Revision as of 10:26, 27 April 2023
Hepatokines (Greek heapto-, liver; and -kinos, movement) are proteins produced by liver cells (hepatocytes) that are secreted into the circulation and function as hormones across the organism. Research is mostly focused on hepatokines that play a role in the regulation of metabolic diseases such as diabetes and fatty liver and include: Adropin, ANGPTL4, Fetuin-A, Fetuin-B, FGF-21, Hepassocin, LECT2, RBP4,Selenoprotein P, Sex hormone-binding globulin.[1]
Function
Hepatokines are hormone-like proteins secreted by hepatocytes, and many have been associated with extra-hepatic metabolic regulation. Through processes like autocrinem, paracrinem, and endocrine signaling, hepatokines can influence metabolic processes.[1] It has been stated that, "hepatocytes secrete more than 560 types of hepatokines, many of which regulate metabolic and inflammatory diseases in the liver or at distant organs through circulation delivery."[2] Hepatocytes can secrete multiple hepatokines into the blood. In particular, these hepatokines, similar to hypothalamic hormones and insulin, are structurally polypeptides, and proteins and are transcribed and expressed by specific genes.
The liver may emit hepatokines to influence energy homeostasis and inflammation under pressure on the metabolism like long-term starvation or over-nutrition. If the liver is unable to fulfill this process, the corresponding disease develops like fatty liver disease from, "impaired hepatic insulin-sensitizing substance production."[2] Hepatokines signal energy status and help regulate nutrient availability to multiple peripheral tissues and the central nervous system (CNS).[2] Hepatokines have been described to be involved in the regulation of energy and nutrient metabolism by acting directly on the liver or on distal target tissues. These proteins regulate glucose and lipid metabolism in the liver but also in the skeletal muscle or the adipose tissue. It is now clear that a single session of exercise is accompanied by the production of liver-secreted proteins. Hepatokines can also mediate the beneficial effects of chronic exercise or, at least, represent biomarkers of training-induced metabolic improvements.[3] Hepatokines directly affect the progression of atherosclerosis by modulating endothelial dysfunction and infiltration of inflammatory cells into vessel walls.[4]
Types
- Fetuin-A was the first hepatokine to be described and correlated with increased inflammation and insulin resistance.[5]
- Fetuin-B significantly increases hepatic steatosis and mediates impaired insulin action and glucose intolerance.[6]
- ANGPTL8/betatrophin, initially proposed for its action on beta cell proliferation, although this effect has recently been brought into question.[5]
- FGF-21 an insulin-sensitising hormone that is an appealing drug target because of its beneficial metabolic actions.[5]
- Adropin is linked to macronutrient intake.[7]
- ANGPTL4 can inhibit lipoprotein lipase and activate cAMP-stimulated lipolysis in adipocytes.[8]
Clinical signifance
Hepatokines can serve as biomarkers and are potential therapeutic targets for metabolic diseases. The liver through execretion of hepatokines regulates the whole bodies metabolism in response to stress signals.[5]
Secreted hepatokines in response to exercise induce favorable metabolic changes in fat, blood vessles, and skeletal muscle that can reduce metabolic diseases.[9]
Although substantial progress has been made in understanding disease-controlled production of hepatokines, there is still so much to discover. There is so much room for discovery. For example, "little is known about the inductive mechanism of transcriptional reprogramming, protein translation, modification, and secretion of hepatokines, particularly through the ER and Golgi, and more.[10] The identification and functional characterization of hepatokines may provide significant insights that could help in better understanding of MetS pathogenesis.[11]
Non-alcoholic fatty liver disease
Hepatokines, sometimes referred to as hepatocytes-derived cytokines[12] have been shown to relate to non-alcoholic fatty liver disease. "Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease.[13] Not only are they involved with metabolic diseseases but they are also linked to diseases of other organs, such as the heart, muscle, bone, and eyes.[10]
See also
References
- ^ a b Meex RC, Watt MJ (September 2017). "Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance". Nature Reviews. Endocrinology. 13 (9): 509–520. doi:10.1038/nrendo.2017.56. PMID 28621339. S2CID 302689.
- ^ a b c Jensen-Cody SO, Potthoff MJ (February 2021). "Hepatokines and metabolism: Deciphering communication from the liver". Molecular Metabolism. 44: 101138. doi:10.1016/j.molmet.2020.101138. PMC 7788242. PMID 33285302.
- ^ Ennequin G, Sirvent P, Whitham M (July 2019). "Role of exercise-induced hepatokines in metabolic disorders" (PDF). American Journal of Physiology. Endocrinology and Metabolism. 317 (1): E11–E24. doi:10.1152/ajpendo.00433.2018. PMID 30964704. S2CID 106409704.
- ^ Yoo HJ, Choi KM (February 2015). "Hepatokines as a Link between Obesity and Cardiovascular Diseases". Diabetes & Metabolism Journal. 39 (1): 10–15. doi:10.4093/dmj.2015.39.1.10. PMC 4342531. PMID 25729707.
- ^ a b c d Iroz A, Couty JP, Postic C (August 2015). "Hepatokines: unlocking the multi-organ network in metabolic diseases". Diabetologia. 58 (8): 1699–1703. doi:10.1007/s00125-015-3634-4. PMID 26032022. S2CID 7141228.
- ^ Yakout SM, Hussein S, Al-Attas OS, Hussain SD, Saadawy GM, Al-Daghri NM (2023). "Hepatokines fetuin A and fetuin B status in women with/without gestational diabetes mellitus". American Journal of Translational Research. 15 (2): 1291–1299. PMC 10006815. PMID 36915725.
- ^ Smati S, Régnier M, Fougeray T, Polizzi A, Fougerat A, Lasserre F, et al. (April 2020). "Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes" (PDF). Diabetes & Metabolism. 46 (2): 129–136. doi:10.1016/j.diabet.2019.05.005. PMID 31163275. S2CID 174810284.
- ^ Zhang Y, Zhu Z, Sun L, Yin W, Liang Y, Chen H, Bi Y, Zhai W, Yin Y, Zhang W (April 2023). "Hepatic G Protein-Coupled Receptor 180 Deficiency Ameliorates High Fat Diet-Induced Lipid Accumulation via the Gi-PKA-SREBP Pathway". Nutrients. 15 (8): 1838. doi:10.3390/nu15081838.
- ^ Seo DY, Park SH, Marquez J, Kwak HB, Kim TN, Bae JH, et al. (January 2021). "Hepatokines as a Molecular Transducer of Exercise". Journal of Clinical Medicine. 10 (3): 385. doi:10.3390/jcm10030385. PMC 7864203. PMID 33498410.
- ^ a b Wang F, So KF, Xiao J, Wang H (January 2021). "Organ-organ communication: The liver's perspective". Theranostics. 11 (7): 3317–3330. doi:10.7150/thno.55795. PMC 7847667. PMID 33537089.
- ^ Esfahani M, Baranchi M, Goodarzi MT (2019). "The implication of hepatokines in metabolic syndrome". Diabetes & Metabolic Syndrome. 13 (4): 2477–2480. doi:10.1016/j.dsx.2019.06.027. PMID 31405664. S2CID 198296158.
- ^ Lu Y, Zheng MH, Wang H (March 2023). "Are hepatocytes endocrine cells?". Metabolism and Target Organ Damage. 3 (1): 3. doi:10.20517/mtod.2023.11. S2CID 257890679.
- ^ Kim TH, Hong DG, Yang YM (December 2021). "Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism". Biomedicines. 9 (12): 1903. doi:10.3390/biomedicines9121903. PMC 8698516. PMID 34944728.
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