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Abstract
PATHOPHYSIOLOGY OF RENIN-ANGIOTENSIN SYSTEM RECEPTORBINDING PROTEIN IN LIFESTYLE DISEASE
Kengo AZUSHIMA, Hiromichi WAKUI, Kouichi TAMURA
Department of Medical Science and Cardiorenal Medicine,
Yokohama City University Graduate School of Medicine
The angiotensin II type 1 receptor (AT1R) is a major player in the signal transduction of the renin-angiotensin
system (RAS), and the overactivation of this signaling contributes to the progression of visceral obesity and metabolic
disorders including insulin resistance. AT1R-associated protein (ATRAP) promotes AT1R internalization along with
the suppression of overactivation of tissue AT1R signaling. Systemic deficiency of ATRAP promoted diet-induced
visceral obesity and insulin resistance, along with exacerbation of adipose tissue inflammation and macrophage
infiltration, and the transplantation of fat pads expressing ATRAP rescued these conditions in this model. Furthermore,
in contrast to ATRAP deficiency, enhancement of ATRAP in adipose tissue ameliorated diet-induced visceral obesity
and insulin resistance via the attenuation of overactivated AT1R signaling and adipose inflammation. It is noteworthy
that both models of ATRAP deficiency and enhancement did not show any evident alterations in physiological
function, including adipose tissue morphology at baseline. These results suggest that ATRAP could inhibit just the
"excessive" activation of RAS, along with preserving the "physiological" activation of RAS that is necessary for the
living body to maintain its homeostasis. Therefore, adipose tissue ATRAP could become an effective and tolerable
therapeutic strategy to treat visceral obesity and metabolic disorders including insulin resistance.
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