FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch
Abstract Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astr...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60747-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849334452331741184 |
|---|---|
| author | Rohit Patel Devin King Brenna LaBarre Hrishikesh Lokhande Danielle Caefer Johnna F. Varghese Keturah Warner Marc A. Bouffard Shrishti Saxena Alena Zhirova Rohit Bakshi Tanuja Chitnis |
| author_facet | Rohit Patel Devin King Brenna LaBarre Hrishikesh Lokhande Danielle Caefer Johnna F. Varghese Keturah Warner Marc A. Bouffard Shrishti Saxena Alena Zhirova Rohit Bakshi Tanuja Chitnis |
| author_sort | Rohit Patel |
| collection | DOAJ |
| description | Abstract Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astrocytes and neural stem cells, but the effect of FABP7 on monocytes is unknown. Here we find elevated levels of FABP7 in the serum and cerebrospinal fluid of patients with secondary progressive MS. Elevated serum FABP7 levels positively correlate with higher disability scores, brain lesion volumes, and lower brain volumes. FABP7 levels are increased in astrocytes from MS postmortem brain lesion. Mechanistically, in vitro treatment of FABP7 induces CD16, CD80 and IL-1β expression in monocytes via increased glycolysis. FABP7-induced gene expression reflects enhanced inflammation, chemotaxis and glucose metabolism in monocytes. In conclusion, we find that FABP7 induces pro-inflammatory profiles in monocytes, correlates with disability and represents a potential biomarker and therapeutic target for progressive MS. |
| format | Article |
| id | doaj-art-3ab2cdf99f554d44b51acf6aeae2cf86 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3ab2cdf99f554d44b51acf6aeae2cf862025-08-20T03:45:34ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-60747-9FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switchRohit Patel0Devin King1Brenna LaBarre2Hrishikesh Lokhande3Danielle Caefer4Johnna F. Varghese5Keturah Warner6Marc A. Bouffard7Shrishti Saxena8Alena Zhirova9Rohit Bakshi10Tanuja Chitnis11Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalDepartment of Neurology, Mass General BrighamAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalAbstract Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astrocytes and neural stem cells, but the effect of FABP7 on monocytes is unknown. Here we find elevated levels of FABP7 in the serum and cerebrospinal fluid of patients with secondary progressive MS. Elevated serum FABP7 levels positively correlate with higher disability scores, brain lesion volumes, and lower brain volumes. FABP7 levels are increased in astrocytes from MS postmortem brain lesion. Mechanistically, in vitro treatment of FABP7 induces CD16, CD80 and IL-1β expression in monocytes via increased glycolysis. FABP7-induced gene expression reflects enhanced inflammation, chemotaxis and glucose metabolism in monocytes. In conclusion, we find that FABP7 induces pro-inflammatory profiles in monocytes, correlates with disability and represents a potential biomarker and therapeutic target for progressive MS.https://doi.org/10.1038/s41467-025-60747-9 |
| spellingShingle | Rohit Patel Devin King Brenna LaBarre Hrishikesh Lokhande Danielle Caefer Johnna F. Varghese Keturah Warner Marc A. Bouffard Shrishti Saxena Alena Zhirova Rohit Bakshi Tanuja Chitnis FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch Nature Communications |
| title | FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch |
| title_full | FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch |
| title_fullStr | FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch |
| title_full_unstemmed | FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch |
| title_short | FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch |
| title_sort | fabp7 is increased in progressive multiple sclerosis and induces a pro inflammatory phenotype in monocytes through a glycolytic switch |
| url | https://doi.org/10.1038/s41467-025-60747-9 |
| work_keys_str_mv | AT rohitpatel fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT devinking fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT brennalabarre fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT hrishikeshlokhande fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT daniellecaefer fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT johnnafvarghese fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT keturahwarner fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT marcabouffard fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT shrishtisaxena fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT alenazhirova fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT rohitbakshi fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch AT tanujachitnis fabp7isincreasedinprogressivemultiplesclerosisandinducesaproinflammatoryphenotypeinmonocytesthroughaglycolyticswitch |