Endotrophin (Mus musculus) TFA is an adipokine, a cleavage fragment derived from Collagen VI, whose levels are elevated in adipose tissue and breast tumors of obese mice. Endotrophin (Mus musculus) TFA activates the TGF-β signaling pathway and reduces the expression of hormone-sensitive lipase. Endotrophin (Mus musculus) TFA induces adipogenesis, lipid accumulation, fibrosis, inflammation, angiogenesis, adipose tissue expansion, epithelial-mesenchymal transition, and insulin resistance; it also induces Cisplatin resistance in cancer cells. Endotrophin (Mus musculus) TFA can be used in research related to metabolic diseases such as obesity and type 2 diabetes, as well as cancers such as breast cancer [1] [2] [3].
In Vivo, Endotrophin (Mus musculus) (200 mg/kg; ad libitum; 8 weeks) TFA administration in high-fat diet-fed mice induces local adipose tissue overexpression that promotes adipogenesis, suppresses lipolysis via reduced HSL phosphorylation, enhances lipid accumulation in adipose tissue, and shifts macrophage polarization toward a pro-inflammatory M1 phenotype[1]. Neutralizing antibody against Endotrophin (Mus musculus) TFA neutralizes endotrophin activity in high-fat diet-induced obese mice and significantly improves insulin sensitivity[2]. Overexpression of Endotrophin (Mus musculus) TFA in MMTV-PyMT transgenic mice significantly increases primary tumor volume, promotes the growth of lung metastatic lesions, and restores tumor growth in collagen VI-deficient MMTV-PyMT mice[2]. Induction of Endotrophin (Mus musculus) TFA confers cisplatin resistance in breast tumor-bearing mice, while neutralizing Endotrophin activity or reducing its levels using TZDs restores cisplatin sensitivity[2]. Endotrophin (Mus musculus) TFA induces adipose tissue fibrosis and inflammation in mice, and causes systemic dyslipidemia, hepatic steatosis and insulin resistance; blocking endogenous Endotrophin with neutralizing antibodies effectively reverses these manifestations[3].
In Vitro, Endotrophin (Mus musculus) (24 h) TFA upregulates the expression of pro-fibrotic (Col1α1, Tgfβ1, TgfβR2) and pro-inflammatory (Nlrp3, Tlr4) genes in the stromal vascular fraction (SVF) isolated from mouse white adipose tissue (WAT)[1]. Endotrophin (Mus musculus) (24-72 h) TFA induces fibrosis in differentiating 3T3-L1 mouse adipocytes, reduces adiponectin expression, promotes adipogenesis, inhibits lipolysis, and increases lipid accumulation[1]. Endotrophin (Mus musculus) (24 h) TFA upregulates the expression of Lox, pro-inflammatory genes (Il-1β, Tnf-α, F4/80), and M1 macrophage markers (Cd40, Cd86) in primary macrophages isolated from mouse white adipose tissue (WAT)[1]. Endotrophin (Mus musculus) TFA is abundantly secreted in fully differentiated 3T3-L1 adipocytes, whereas no secreted level is detected in 3T3-L1 preadipocytes[3].
References:
[1]. Zhao Y, et al. Divergent functions of endotrophin on different cell populations in adipose tissue. Am J Physiol Endocrinol Metab. 2016;311(6):E952-E963.
[2]. Sun K, et al. Endotrophin, a multifaceted player in metabolic dysregulation and cancer progression, is a predictive biomarker for the response to PPARγ agonist treatment. Diabetologia. 2017;60(1):24-29.
[3]. Sun K, et al. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nat Commun. 2014;5:3485. Published 2014 Mar 19.
In Vivo, Endotrophin (Mus musculus) (200 mg/kg; ad libitum; 8 weeks) TFA administration in high-fat diet-fed mice induces local adipose tissue overexpression that promotes adipogenesis, suppresses lipolysis via reduced HSL phosphorylation, enhances lipid accumulation in adipose tissue, and shifts macrophage polarization toward a pro-inflammatory M1 phenotype[1]. Neutralizing antibody against Endotrophin (Mus musculus) TFA neutralizes endotrophin activity in high-fat diet-induced obese mice and significantly improves insulin sensitivity[2]. Overexpression of Endotrophin (Mus musculus) TFA in MMTV-PyMT transgenic mice significantly increases primary tumor volume, promotes the growth of lung metastatic lesions, and restores tumor growth in collagen VI-deficient MMTV-PyMT mice[2]. Induction of Endotrophin (Mus musculus) TFA confers cisplatin resistance in breast tumor-bearing mice, while neutralizing Endotrophin activity or reducing its levels using TZDs restores cisplatin sensitivity[2]. Endotrophin (Mus musculus) TFA induces adipose tissue fibrosis and inflammation in mice, and causes systemic dyslipidemia, hepatic steatosis and insulin resistance; blocking endogenous Endotrophin with neutralizing antibodies effectively reverses these manifestations[3].
In Vitro, Endotrophin (Mus musculus) (24 h) TFA upregulates the expression of pro-fibrotic (Col1α1, Tgfβ1, TgfβR2) and pro-inflammatory (Nlrp3, Tlr4) genes in the stromal vascular fraction (SVF) isolated from mouse white adipose tissue (WAT)[1]. Endotrophin (Mus musculus) (24-72 h) TFA induces fibrosis in differentiating 3T3-L1 mouse adipocytes, reduces adiponectin expression, promotes adipogenesis, inhibits lipolysis, and increases lipid accumulation[1]. Endotrophin (Mus musculus) (24 h) TFA upregulates the expression of Lox, pro-inflammatory genes (Il-1β, Tnf-α, F4/80), and M1 macrophage markers (Cd40, Cd86) in primary macrophages isolated from mouse white adipose tissue (WAT)[1]. Endotrophin (Mus musculus) TFA is abundantly secreted in fully differentiated 3T3-L1 adipocytes, whereas no secreted level is detected in 3T3-L1 preadipocytes[3].
References:
[1]. Zhao Y, et al. Divergent functions of endotrophin on different cell populations in adipose tissue. Am J Physiol Endocrinol Metab. 2016;311(6):E952-E963.
[2]. Sun K, et al. Endotrophin, a multifaceted player in metabolic dysregulation and cancer progression, is a predictive biomarker for the response to PPARγ agonist treatment. Diabetologia. 2017;60(1):24-29.
[3]. Sun K, et al. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nat Commun. 2014;5:3485. Published 2014 Mar 19.