Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice
Abstract Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-01-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-020-03367-z |
| _version_ | 1819057828722114560 |
|---|---|
| author | Jung-Hwan Baek Da-Hyun Kim Jaegyeong Lee Seok-Jun Kim Kyung-Hee Chun |
| author_facet | Jung-Hwan Baek Da-Hyun Kim Jaegyeong Lee Seok-Jun Kim Kyung-Hee Chun |
| author_sort | Jung-Hwan Baek |
| collection | DOAJ |
| description | Abstract Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPARγ, C/EBPα, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPARγ. Galectin-1 overexpression resulted in increased PPARγ expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1 −/−) mice and fed a 60% HFD. After 10 weeks, Lgals1 −/− mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1 −/−mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1 −/− mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNFα, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1 −/− mice. In addition, Lgals1−/−mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application. |
| first_indexed | 2024-12-21T13:45:31Z |
| format | Article |
| id | doaj.art-6f5f61f9bab34868a567cb80de0bdfc0 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-21T13:45:31Z |
| publishDate | 2021-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6f5f61f9bab34868a567cb80de0bdfc02022-12-21T19:01:53ZengNature Publishing GroupCell Death and Disease2041-48892021-01-0112111110.1038/s41419-020-03367-zGalectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in miceJung-Hwan Baek0Da-Hyun Kim1Jaegyeong Lee2Seok-Jun Kim3Kyung-Hee Chun4Department of Biochemistry and Molecular Biology, Yonsei University College of MedicineDepartment of Biochemistry and Molecular Biology, Yonsei University College of MedicineDepartment of Biochemistry and Molecular Biology, Yonsei University College of MedicineDepartment of Biomedical Science & BK21 FOUR Educational Research Group for Age-associated Disorder Control Technology, Chosun UniversityDepartment of Biochemistry and Molecular Biology, Yonsei University College of MedicineAbstract Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPARγ, C/EBPα, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPARγ. Galectin-1 overexpression resulted in increased PPARγ expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1 −/−) mice and fed a 60% HFD. After 10 weeks, Lgals1 −/− mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1 −/−mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1 −/− mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNFα, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1 −/− mice. In addition, Lgals1−/−mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.https://doi.org/10.1038/s41419-020-03367-z |
| spellingShingle | Jung-Hwan Baek Da-Hyun Kim Jaegyeong Lee Seok-Jun Kim Kyung-Hee Chun Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice Cell Death and Disease |
| title | Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice |
| title_full | Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice |
| title_fullStr | Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice |
| title_full_unstemmed | Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice |
| title_short | Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice |
| title_sort | galectin 1 accelerates high fat diet induced obesity by activation of peroxisome proliferator activated receptor gamma pparγ in mice |
| url | https://doi.org/10.1038/s41419-020-03367-z |
| work_keys_str_mv | AT junghwanbaek galectin1accelerateshighfatdietinducedobesitybyactivationofperoxisomeproliferatoractivatedreceptorgammapparginmice AT dahyunkim galectin1accelerateshighfatdietinducedobesitybyactivationofperoxisomeproliferatoractivatedreceptorgammapparginmice AT jaegyeonglee galectin1accelerateshighfatdietinducedobesitybyactivationofperoxisomeproliferatoractivatedreceptorgammapparginmice AT seokjunkim galectin1accelerateshighfatdietinducedobesitybyactivationofperoxisomeproliferatoractivatedreceptorgammapparginmice AT kyungheechun galectin1accelerateshighfatdietinducedobesitybyactivationofperoxisomeproliferatoractivatedreceptorgammapparginmice |