دورية أكاديمية
Reduction of TIP47 improves hepatic steatosis and glucose homeostasis in mice.
| العنوان: | Reduction of TIP47 improves hepatic steatosis and glucose homeostasis in mice. |
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| المؤلفون: | Carr RM; University of Pennsylvania, Perelman School of Medicine, Department of Medicine, Gastroenterology Division, Philadelphia, Pennsylvania 19104, USA., Patel RT, Rao V, Dhir R, Graham MJ, Crooke RM, Ahima RS |
| المصدر: | American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2012 Apr 15; Vol. 302 (8), pp. R996-1003. Date of Electronic Publication: 2012 Feb 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1490 (Electronic) Linking ISSN: 03636119 NLM ISO Abbreviation: Am J Physiol Regul Integr Comp Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society |
| مواضيع طبية MeSH: | Blood Glucose/*metabolism , Carrier Proteins/*metabolism , Fatty Liver/*metabolism , Liver/*metabolism, Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Animals ; Carrier Proteins/genetics ; Diet, High-Fat ; Fatty Liver/pathology ; Fatty Liver/therapy ; Insulin/metabolism ; Insulin Resistance/physiology ; Liver/drug effects ; Liver/pathology ; Mice ; Oligonucleotides, Antisense/pharmacology ; Oligonucleotides, Antisense/therapeutic use ; Perilipin-3 ; Triglycerides/metabolism |
| مستخلص: | Lipid droplets in the liver are coated with the perilipin family of proteins, notably adipocyte differentiation-related protein (ADRP) and tail-interacting protein of 47 kDa (TIP47). ADRP is increased in hepatic steatosis and is associated with hyperlipidemia, insulin resistance, and glucose intolerance. We have shown that reducing ADRP in the liver via antisense oligonucleotide (ASO) treatment attenuates steatosis and improves insulin sensitivity and glucose tolerance. We hypothesized that TIP47 has similar effects on hepatic lipid and glucose metabolism. We found that TIP47 mRNA and protein levels were increased in response to a high-fat diet (HFD) in C57BL/6J mice. TIP47 ASO treatment decreased liver TIP47 mRNA and protein levels without altering ADRP levels. Low-dose TIP47 ASO (15 mg/kg) and high-dose TIP47 ASO (50 mg/kg) decreased triglyceride content in the liver by 35% and 52%, respectively. Liver histology showed a drastic reduction in hepatic steatosis following TIP47 ASO treatment. The high dose of TIP47 ASO significantly blunted hepatic triglyceride secretion, improved glucose tolerance, and increased insulin sensitivity in liver, adipose tissue, and muscle. These findings show that TIP47 affects hepatic lipid and glucose metabolism and may be a target for the treatment of nonalcoholic fatty liver and related metabolic disorders. |
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| معلومات مُعتمدة: | P01 DK049210 United States DK NIDDK NIH HHS; T32-DK-007066 United States DK NIDDK NIH HHS; P30-DK-50306 United States DK NIDDK NIH HHS; P01-DK-049210 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Blood Glucose) 0 (Carrier Proteins) 0 (Insulin) 0 (Oligonucleotides, Antisense) 0 (Perilipin-3) 0 (Plin3 protein, mouse) 0 (Triglycerides) |
| تواريخ الأحداث: | Date Created: 20120302 Date Completed: 20120618 Latest Revision: 20230606 |
| رمز التحديث: | 20230606 |
| مُعرف محوري في PubMed: | PMC3330768 |
| DOI: | 10.1152/ajpregu.00177.2011 |
| PMID: | 22378776 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1490 |
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| DOI: | 10.1152/ajpregu.00177.2011 |