Mice with Fabp4-Cre Ablation of Arid5b are Resistant to Diet-Induced Obesity and Hepatic Steatosis
| Autor: | Shu-Lian Li, Garrett P. Larson, Keiichi Itakura, Robert H. Whitson, Guoxiang Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Subcutaneous Fat Adipose tissue 030209 endocrinology & metabolism Inflammation White adipose tissue Biology Diet High-Fat Fatty Acid-Binding Proteins Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Internal medicine medicine Animals Obesity Molecular Biology Triglyceride Sequence Analysis RNA Gene Expression Profiling food and beverages nutritional and metabolic diseases Lipid metabolism medicine.disease Lipid Metabolism Phenotype DNA-Binding Proteins Fatty Liver Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Gene Expression Regulation Adipogenesis lipids (amino acids peptides and proteins) Steatosis medicine.symptom hormones hormone substitutes and hormone antagonists Gene Deletion Transcription Factors |
| Zdroj: | Mol Cell Endocrinol |
| Popis: | Mice with global deletion of Arid5b expression are lean and resistant to diet-induced obesity, and Arid5b is required for adipogenesis in a variety of in vitro models. To determine whether the lean phenotype of Arid5b(−/−) mice can be explained by its absence in adipose tissues, we generated mice with Fabp4-mediated ablation of Arid5b. Arid5b expression was ablated in adipocytes, from Fabp4-CRE(pos); Arid5b(FLOX/FLOX) (FSKO) mice. FSKO mice were not lean when maintained on standard chow, but males were resistant to weight gains when placed on high-fat diets (HFD). This was mainly due to decreased lipid accumulation in subcutaneous (inguinal) white adipose tissue (IWAT), and the liver. Lipid accumulation proceeded normally in gonadal WAT (GWAT) and glucose intolerance developed to the same degree in FSKO and WT controls when subjected to HFD. CD68-positive macrophages were also significantly reduced in both inguinal and gonadal fat depots. RNA-Seq analysis of IWAT adipocytes from FSKO mice on HFD revealed significant decreases in the expression of genes associated with inflammation. Although Arid5b expression was normal in livers of FSKO mice, tissue weight gains and triglyceride accumulation, and expression of genes involved in lipid metabolism were markedly reduced in livers of FSKO mice on HFD. These results suggest that Arid5b plays a critical role in lipid accumulation in specific WAT depots, and in the inflammatory signaling from WAT depots to liver that lead to lipid accumulation and hepatic steatosis. |
| Databáze: | OpenAIRE |
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