Obesity-induced TRB3 negatively regulates Brown adipose tissue function in mice
| Autor: | Ha-Won Jeong, Ho-Jin Koh, Ran Hee Choi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Biophysics Mice Obese Cell Cycle Proteins Type 2 diabetes Biology Diet High-Fat Biochemistry Article Mice 03 medical and health sciences 0302 clinical medicine Adipose Tissue Brown Internal medicine Brown adipose tissue medicine Animals Obesity Molecular Biology Incubation Cells Cultured Uncoupling Protein 1 Mice Knockout Thermogenesis Cell Biology Endoplasmic Reticulum Stress medicine.disease Mice Inbred C57BL Disease Models Animal Insulin receptor 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis Unfolded protein response biology.protein Function (biology) Signal Transduction |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.01.103 |
| Popis: | Brown adipose tissue (BAT) and stimulating adaptive thermogenesis have been implicated as anti-obese and anti-diabetic tissues due to their ability to dissipate energy as heat by the expression of UCP1. We have recently demonstrated that TRB3 impairs differentiation of brown preadipocytes via inhibiting insulin signaling. However, the roles of the protein in BAT function and thermogenesis in vivo have not yet been established. For this study we tested the hypothesis that TRB3 mediates obesity- and diabetes-induced impairments in BAT differentiation and function, and that inhibition of TRB3 improves BAT function. TRB3 expression was increased in BAT from high-fat fed mice and ob/ob mice, which was associated with decreased UCP1 expression. Incubation of brown adipocytes with palmitate increased TRB3 expression and decreased UCP1. Knockout of TRB3 in mice displayed higher UCP1 expression in BAT and cold resistance. Incubation of brown adipocytes with ER stressors increased TRB3 but decreased UCP1 and ER stress markers were elevated in BAT from high-fat fed mice and ob/ob mice. Finally, high-fat feeding in TRB3KO mice were protected from obesity-induced glucose intolerance and displayed cold resistance and higher expression of BAT-specific markers. These data demonstrate that high-fat feeding and obesity increase TRB3 in BAT, resulting in impaired tissue function. |
| Databáze: | OpenAIRE |
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