Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease?
<h4>Background</h4>Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the r...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4fd2416859f4431aa48d925e75ea8bf8 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4fd2416859f4431aa48d925e75ea8bf8 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4fd2416859f4431aa48d925e75ea8bf82021-11-25T06:19:14ZIs there a role for neuregulin 4 in human nonalcoholic fatty liver disease?1932-620310.1371/journal.pone.0251822https://doaj.org/article/4fd2416859f4431aa48d925e75ea8bf82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251822https://doaj.org/toc/1932-6203<h4>Background</h4>Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients.<h4>Methods</h4>Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed.<h4>Results</h4>Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls.<h4>Conclusion</h4>Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD.Toon J I De MunckMarkus BoeschPauline VerhaeghAd A M MascleeDaisy JonkersJos F van PeltJohannie du PlessisHannelie KorfFrederik NevensGer H KoekSchalk Van der MerweJef VerbeekPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251822 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Toon J I De Munck Markus Boesch Pauline Verhaegh Ad A M Masclee Daisy Jonkers Jos F van Pelt Johannie du Plessis Hannelie Korf Frederik Nevens Ger H Koek Schalk Van der Merwe Jef Verbeek Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| description |
<h4>Background</h4>Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients.<h4>Methods</h4>Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed.<h4>Results</h4>Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls.<h4>Conclusion</h4>Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD. |
| format |
article |
| author |
Toon J I De Munck Markus Boesch Pauline Verhaegh Ad A M Masclee Daisy Jonkers Jos F van Pelt Johannie du Plessis Hannelie Korf Frederik Nevens Ger H Koek Schalk Van der Merwe Jef Verbeek |
| author_facet |
Toon J I De Munck Markus Boesch Pauline Verhaegh Ad A M Masclee Daisy Jonkers Jos F van Pelt Johannie du Plessis Hannelie Korf Frederik Nevens Ger H Koek Schalk Van der Merwe Jef Verbeek |
| author_sort |
Toon J I De Munck |
| title |
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| title_short |
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| title_full |
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| title_fullStr |
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| title_full_unstemmed |
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| title_sort |
is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/4fd2416859f4431aa48d925e75ea8bf8 |
| work_keys_str_mv |
AT toonjidemunck istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT markusboesch istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT paulineverhaegh istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT adammasclee istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT daisyjonkers istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT josfvanpelt istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT johannieduplessis istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT hanneliekorf istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT frederiknevens istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT gerhkoek istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT schalkvandermerwe istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease AT jefverbeek istherearoleforneuregulin4inhumannonalcoholicfattyliverdisease |
| _version_ |
1718413924011868160 |