Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption
Abstract Tissue inhibitor of metalloproteases (TIMPs) are inhibitors of matrix metalloproteinases (MMPs) that regulate tissue extracellular matrix (ECM) turnover. TIMP4 is highly expressed in adipose tissue, its levels are further elevated following high-fat diet, but its role in obesity is unknown....
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/fa68f747eb244e7984495198cb3a085e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:fa68f747eb244e7984495198cb3a085e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:fa68f747eb244e7984495198cb3a085e2021-12-02T16:06:06ZAbsence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption10.1038/s41598-017-05951-42045-2322https://doaj.org/article/fa68f747eb244e7984495198cb3a085e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05951-4https://doaj.org/toc/2045-2322Abstract Tissue inhibitor of metalloproteases (TIMPs) are inhibitors of matrix metalloproteinases (MMPs) that regulate tissue extracellular matrix (ECM) turnover. TIMP4 is highly expressed in adipose tissue, its levels are further elevated following high-fat diet, but its role in obesity is unknown. Eight-week old wild-type (WT) and Timp4-knockout (Timp4 −/−) mice received chow or high fat diet (HFD) for twelve weeks. Timp4 −/− mice exhibited a higher food intake but lower body fat gain. Adipose tissue of Timp4 −/– -HFD mice showed reduced hypertrophy and fibrosis compared to WT-HFD mice. Timp4 −/– -HFD mice were also protected from HFD-induced liver and skeletal muscle triglyceride accumulation and dyslipidemia. Timp4 −/−-HFD mice exhibited reduced basic metabolic rate and energy expenditure, but increased respiratory exchange ratio. Increased free fatty acid excretion was detected in Timp4 −/−-HFD compared to WT-HFD mice. CD36 protein, the major fatty acid transporter in the small intestine, increased with HFD in WT but not in Timp4 −/− mice, despite a similar rise in Cd36 mRNA in both genotypes. Consistently, HFD increased enterocyte lipid content only in WT but not in Timp4 −/− mice. Our study reveals that absence of TIMP4 can impair lipid absorption and the high fat diet-induced obesity in mice possibly by regulating the proteolytic processing of CD36 protein in the intestinal enterocytes.Siva S. V. P. SakamuriRussell WattsAbhijit TakawaleXiuhua WangSamuel Hernandez-AnzaldoWesam BahithamCarlos Fernandez-PatronRichard LehnerZamaneh KassiriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Siva S. V. P. Sakamuri Russell Watts Abhijit Takawale Xiuhua Wang Samuel Hernandez-Anzaldo Wesam Bahitham Carlos Fernandez-Patron Richard Lehner Zamaneh Kassiri Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| description |
Abstract Tissue inhibitor of metalloproteases (TIMPs) are inhibitors of matrix metalloproteinases (MMPs) that regulate tissue extracellular matrix (ECM) turnover. TIMP4 is highly expressed in adipose tissue, its levels are further elevated following high-fat diet, but its role in obesity is unknown. Eight-week old wild-type (WT) and Timp4-knockout (Timp4 −/−) mice received chow or high fat diet (HFD) for twelve weeks. Timp4 −/− mice exhibited a higher food intake but lower body fat gain. Adipose tissue of Timp4 −/– -HFD mice showed reduced hypertrophy and fibrosis compared to WT-HFD mice. Timp4 −/– -HFD mice were also protected from HFD-induced liver and skeletal muscle triglyceride accumulation and dyslipidemia. Timp4 −/−-HFD mice exhibited reduced basic metabolic rate and energy expenditure, but increased respiratory exchange ratio. Increased free fatty acid excretion was detected in Timp4 −/−-HFD compared to WT-HFD mice. CD36 protein, the major fatty acid transporter in the small intestine, increased with HFD in WT but not in Timp4 −/− mice, despite a similar rise in Cd36 mRNA in both genotypes. Consistently, HFD increased enterocyte lipid content only in WT but not in Timp4 −/− mice. Our study reveals that absence of TIMP4 can impair lipid absorption and the high fat diet-induced obesity in mice possibly by regulating the proteolytic processing of CD36 protein in the intestinal enterocytes. |
| format |
article |
| author |
Siva S. V. P. Sakamuri Russell Watts Abhijit Takawale Xiuhua Wang Samuel Hernandez-Anzaldo Wesam Bahitham Carlos Fernandez-Patron Richard Lehner Zamaneh Kassiri |
| author_facet |
Siva S. V. P. Sakamuri Russell Watts Abhijit Takawale Xiuhua Wang Samuel Hernandez-Anzaldo Wesam Bahitham Carlos Fernandez-Patron Richard Lehner Zamaneh Kassiri |
| author_sort |
Siva S. V. P. Sakamuri |
| title |
Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| title_short |
Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| title_full |
Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| title_fullStr |
Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| title_full_unstemmed |
Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| title_sort |
absence of tissue inhibitor of metalloproteinase-4 (timp4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/fa68f747eb244e7984495198cb3a085e |
| work_keys_str_mv |
AT sivasvpsakamuri absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT russellwatts absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT abhijittakawale absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT xiuhuawang absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT samuelhernandezanzaldo absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT wesambahitham absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT carlosfernandezpatron absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT richardlehner absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption AT zamanehkassiri absenceoftissueinhibitorofmetalloproteinase4timp4ameliorateshighfatdietinducedobesityinmiceduetodefectivelipidabsorption |
| _version_ |
1718385124488249344 |