TMBIM1 is an inhibitor of adipogenesis and its depletion promotes adipocyte hyperplasia and improves obesity-related metabolic disease

Zhao, Guang‐Nian; Tian, Zheng-Wei; Tian, Tian; Zhu, Zhi-Peng; Zhao, Weina; Tian, Han; Xu, Cheng; Hu, Fengjiao; Hu, Manli; Shen, Tian; Ding, Ting; Chen, Siping; Ji, Yan‐Xiao; Zhang, Peng; Zhang, Xiaojing; She, Zhi‐Gang; Yu-feng, Yuan; Chen, Wenping; Bai, Lan; Li, Hongliang

doi:10.1016/j.cmet.2021.05.014

Cited by 37 publications

(32 citation statements)

References 49 publications

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“…Rodent models of high-fat diet (HFD)-induced obesity have been extensively applied to study human metabolic disorders ( 6 – 9 ). However, these rodent models are largely limited by their capacity to accurately mimic the metabolic aspects of human diseases ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model

Chen

et al. 2022

Front. Endocrinol.

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Canine models are increasingly being used in metabolic studies due to their physiological similarity with humans. The present study aimed to identify changes in metabolic pathways and biomarkers with potential clinical utility in a canine model of obesity and metabolic disorders induced by a high-fat diet (HFD). Eighteen male beagles were included in this study, 9 of which were fed a HFD for 24 weeks, and the remaining 9 were fed normal chow (NC) during the same period. Plasma and urine samples were collected at weeks 12 and 24 for untargeted metabolomic analysis. Dogs fed a HFD showed a gradual body weight increase during the feeding period and had hyperlipidemia, increased leukocyte counts, and impaired insulin sensitivity at week 24. Plasma and urine metabonomics analysis displayed clear separations between the HFD-fed and NC-fed dogs. A total of 263 plasma metabolites varied between the two groups, including stearidonic acid, linolenic acid, carnitine, long-chain ceramide, 3-methylxanthine, and theophylline, which are mainly engaged in fatty acid metabolism, sphingolipid metabolism, and caffeine metabolism. A total of 132 urine metabolites related to HFD-induced obesity and metabolic disorders were identified, including 3-methylxanthine, theophylline, pyridoxal 5’-phosphate, and harmine, which participate in pathways such as caffeine metabolism and vitamin digestion and absorption. Eight metabolites with increased abundance (e.g., 3-methylxanthine, theophylline, and harmine) and 4 metabolites with decreased abundance (e.g., trigonelline) in both the plasma and urine of the HFD-fed dogs were identified. In conclusion, the metabolomic analysis revealed molecular events underlying a canine HFD model and identified several metabolites as potential targets for the prevention and treatment of obesity-related metabolic disorders.

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Section: Introductionmentioning

confidence: 99%

Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model

Chen

et al. 2022

Front. Endocrinol.

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“…TMBIM1 is identi ed as a lysosomal transmembrane protein which inhibits adipogenesis and improves obesity-related metabolic disease by reducing the stability of PPARγ (12). In addition, TMBIM1 is involved in the prevention of non-alcoholic steatohepatitis, metabolic syndrome and cardiomyopathy (11,12). However, few studies have linked TMBIM1 with the formation and progression of human tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Hongliang Li et.al. reported that TMBIM1 inhibits adipocyte proliferation and improves obesity-related metabolic diseases by promoting lysosomal degradation of TLR4 (11,12). Lysosomal degradation is a fundamental process during autophagy which is a self-digesting process.…”

Section: Introductionmentioning

confidence: 99%

TMBIM1 promotes EMT by stimulating autophagic degradation of E-cadherin via AMPK/mTOR/ULK1 axis in human gliomas

Gao

Liu

Zhang

et al. 2022

Preprint

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Background Gliomas are the most common malignant tumors of the central nervous system in adults, glioblastoma is notorious for its highly metastatic and recurrent, accounting for approximately 50% of all gliomas. Exploring its molecular mechanism is urgently needed for the treatment and prognosis evaluation of gliomas. Transmembrane BAX inhibitor motif-containing 1 (TMBIM1) has been reported to be associated with non-alcoholic steatohepatitis, tumor and other diseases. However, the role of TMBIM1 in GBM and the underlying mechanisms remains unclear.MethodsThe expression level and prognostic value of TMBIM1 in gliomas were investigated by public datasets, and further confirmed by western blot and immunohistochemistry (IHC) in our tissues. Intracranial xenograft model, IHC and western blot were used to evaluate the functional role of TMBIM1.ResultsTMBIM1 was over-expressed in GBM, and its high expression reduced the survival time of glioma patients. TMBIM1 induced EMT and autophagy, and inhibition of autophagy reverses TMBIM1-regulated EMT in vitro and in vivo. Intracranial xenograft model showed the survival time of mice in TMBIM1 knockdown group treated with chloroquine (CQ)was significantly prolonged. The loss of E-cadherin expression is considered the foundation of EMT, and we subsequently demonstrated that TMBIM1 stimulating autophagic degradation of E-cadherin via AMPK/mTOR/ULK1 axis. ConclusionOur study provides a novel mechanism for the regulation of EMT in the process of gliomas metastasis, indicating that inhibition of TMBIM1 activity to attenuate autophagy may be a potential strategy for the treatment of gliomas.

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“…Most ingested fat is diverted to adipose tissue or working muscle for storage or oxidation, but fat stored in white adipose tissue undergoes lipolysis to release fatty acids. [ 29 ] Excess fatty acids contribute to accumulation of very large amounts of TGs in hepatocytes and frequently lead to steatosis in the liver. [ 30 ] In this study, breviscapine reduced the hepatic lipid content in PO‐treated hepatocytes and the livers of diet‐induced mice.…”

Section: Discussionmentioning

confidence: 99%

Breviscapine alleviates NASH by inhibiting TGF‐β‐activated kinase 1‐dependent signaling

et al. 2021

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Background and Aims: NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism.However, the anti-NASH efficacy and mechanisms of breviscapine have not yet been characterized. Approach and Results:We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high-fat diet, a high-fat/high-cholesterol diet, or a methionineand choline-deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA-sequencing and multiomics analyses further indicated that the

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TMBIM1 is an inhibitor of adipogenesis and its depletion promotes adipocyte hyperplasia and improves obesity-related metabolic disease

Cited by 37 publications

References 49 publications

Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model

Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model

TMBIM1 promotes EMT by stimulating autophagic degradation of E-cadherin via AMPK/mTOR/ULK1 axis in human gliomas

Breviscapine alleviates NASH by inhibiting TGF‐β‐activated kinase 1‐dependent signaling

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