{"corpus_id":42061844,"paper_sha":null,"doi":"10.1038/s41598-017-05951-4","arxiv_id":null,"pmid":28740132,"pmcid":"5524827","mag_id":2736820616,"dblp_id":null,"acl_id":null,"title":"Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption","year":2017,"publication_date":"2017-07-24","venue":"Scientific Reports","journal":{"name":"Scientific Reports","pages":null,"volume":"7"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":42,"citation_count":36,"influential_citation_count":1,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adipose Tissue","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D000273"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"CD36 Antigens","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D018955"},{"d":"Diet, High-Fat","mj":false,"qs":[{"q":"adverse effects","mj":true,"ui":"Q000009"}],"ui":"D059305"},{"d":"Dyslipidemias","mj":false,"qs":[{"q":"etiology","mj":true,"ui":"Q000209"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D050171"},{"d":"Energy Metabolism","mj":false,"ui":"D004734"},{"d":"Fatty Liver","mj":false,"qs":[{"q":"etiology","mj":true,"ui":"Q000209"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D005234"},{"d":"Inflammation","mj":false,"qs":[{"q":"etiology","mj":true,"ui":"Q000209"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D007249"},{"d":"Lipids","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D008055"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred C57BL","mj":false,"ui":"D008810"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"Obesity","mj":false,"qs":[{"q":"etiology","mj":true,"ui":"Q000209"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D009765"},{"d":"Tissue Inhibitor of Metalloproteinases","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D019714"},{"d":"Tissue Inhibitor of Metalloproteinase-4","mj":false,"ui":"D000097792"}],"chemicals":[{"n":"CD36 Antigens","ui":"D018955","reg":"0"},{"n":"Lipids","ui":"D008055","reg":"0"},{"n":"Tissue Inhibitor of Metalloproteinases","ui":"D019714","reg":"0"},{"n":"Tissue Inhibitor of Metalloproteinase-4","ui":"D000097792","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"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.","claims":[{"public_id":"cl_ea1ac16032956f9dc5ff0a7db01956ab","status":"active","text":"Absence of TIMP4 is associated with impaired intestinal lipid absorption, including increased free fatty acid excretion, preserved Cd36 mRNA induction without CD36 protein increase, and reduced enterocyte lipid content under high-fat diet.","confidence":0.99,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ea1ac16032956f9dc5ff0a7db01956ab"},{"public_id":"cl_c8d4a0234bbf3e84d40f553249292d5e","status":"active","text":"Absence of TIMP4 reduces high fat diet-induced body fat gain in mice despite higher food 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