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Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity.
J Am Heart Assoc. 2013 Jul 31; 2(4):e000312.JA

Abstract

BACKGROUND

Metabolic disorders with visceral obesity have become a major medical problem associated with the development of hypertension, type 2 diabetes, and dyslipidemia and, ultimately, life-threatening cardiovascular and renal diseases. Adipose tissue dysfunction has been proposed as the cause of visceral obesity-related metabolic disorders, moving the tissue toward a proinflammatory phenotype.

METHODS AND RESULTS

Here we first report that adipose tissues from patients and mice with metabolic disorders exhibit decreased expression of ATRAP/Agtrap, which is a specific binding modulator of the angiotensin II type 1 receptor, despite its abundant expression in adipose tissues from normal human and control mice. Subsequently, to examine a functional role of ATRAP in the pathophysiology of metabolic disorders, we produced homozygous ATRAP deficient (Agtrap(-/-)) mice, which exhibited largely normal physiological phenotype at baseline. Under dietary high fat loading, Agtrap(-/-) mice displayed systemic metabolic dysfunction, characterized by an increased accumulation of pad fat, hypertension, dyslipidemia, and insulin resistance, along with adipose tissue inflammation. Conversely, subcutaneous transplantation of donor fat pads overexpressing ATRAP derived from Agtrap transgenic mice to Agtrap(-/-) recipient mice improved the systemic metabolic dysfunction.

CONCLUSIONS

These results demonstrate that Agtrap(-/-) mice are an effective model of metabolic disorders with visceral obesity and constitute evidence that ATRAP plays a protective role against insulin resistance, suggesting a new therapeutic target in metabolic disorders. Identification of ATRAP as a novel receptor binding modulator of adipose tissue inflammation not only has cardiovascular significance but may have generalized implication in the regulation of tissue function.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23902639

Citation

Maeda, Akinobu, et al. "Angiotensin Receptor-binding Protein ATRAP/Agtrap Inhibits Metabolic Dysfunction With Visceral Obesity." Journal of the American Heart Association, vol. 2, no. 4, 2013, pp. e000312.
Maeda A, Tamura K, Wakui H, et al. Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. J Am Heart Assoc. 2013;2(4):e000312.
Maeda, A., Tamura, K., Wakui, H., Dejima, T., Ohsawa, M., Azushima, K., Kanaoka, T., Uneda, K., Matsuda, M., Yamashita, A., Miyazaki, N., Yatsu, K., Hirawa, N., Toya, Y., & Umemura, S. (2013). Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. Journal of the American Heart Association, 2(4), e000312. https://doi.org/10.1161/JAHA.113.000312
Maeda A, et al. Angiotensin Receptor-binding Protein ATRAP/Agtrap Inhibits Metabolic Dysfunction With Visceral Obesity. J Am Heart Assoc. 2013 Jul 31;2(4):e000312. PubMed PMID: 23902639.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. AU - Maeda,Akinobu, AU - Tamura,Kouichi, AU - Wakui,Hiromichi, AU - Dejima,Toru, AU - Ohsawa,Masato, AU - Azushima,Kengo, AU - Kanaoka,Tomohiko, AU - Uneda,Kazushi, AU - Matsuda,Miyuki, AU - Yamashita,Akio, AU - Miyazaki,Nobuko, AU - Yatsu,Keisuke, AU - Hirawa,Nobuhito, AU - Toya,Yoshiyuki, AU - Umemura,Satoshi, Y1 - 2013/07/31/ PY - 2013/8/2/entrez PY - 2013/8/2/pubmed PY - 2014/5/3/medline KW - adipocyte KW - angiotensin receptor KW - inflammation KW - insulin resistance KW - transplantation SP - e000312 EP - e000312 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 2 IS - 4 N2 - BACKGROUND: Metabolic disorders with visceral obesity have become a major medical problem associated with the development of hypertension, type 2 diabetes, and dyslipidemia and, ultimately, life-threatening cardiovascular and renal diseases. Adipose tissue dysfunction has been proposed as the cause of visceral obesity-related metabolic disorders, moving the tissue toward a proinflammatory phenotype. METHODS AND RESULTS: Here we first report that adipose tissues from patients and mice with metabolic disorders exhibit decreased expression of ATRAP/Agtrap, which is a specific binding modulator of the angiotensin II type 1 receptor, despite its abundant expression in adipose tissues from normal human and control mice. Subsequently, to examine a functional role of ATRAP in the pathophysiology of metabolic disorders, we produced homozygous ATRAP deficient (Agtrap(-/-)) mice, which exhibited largely normal physiological phenotype at baseline. Under dietary high fat loading, Agtrap(-/-) mice displayed systemic metabolic dysfunction, characterized by an increased accumulation of pad fat, hypertension, dyslipidemia, and insulin resistance, along with adipose tissue inflammation. Conversely, subcutaneous transplantation of donor fat pads overexpressing ATRAP derived from Agtrap transgenic mice to Agtrap(-/-) recipient mice improved the systemic metabolic dysfunction. CONCLUSIONS: These results demonstrate that Agtrap(-/-) mice are an effective model of metabolic disorders with visceral obesity and constitute evidence that ATRAP plays a protective role against insulin resistance, suggesting a new therapeutic target in metabolic disorders. Identification of ATRAP as a novel receptor binding modulator of adipose tissue inflammation not only has cardiovascular significance but may have generalized implication in the regulation of tissue function. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/23902639/Angiotensin_receptor_binding_protein_ATRAP/Agtrap_inhibits_metabolic_dysfunction_with_visceral_obesity_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.113.000312?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -