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Activation of systemic, but not local, renin-angiotensin system is associated with up-regulation of TNF-α during prolonged fasting in northern elephant seal pups

Year: 2013

Type: article

Abstract: Northern elephant seal pups naturally endure a 2-3 month post-weaning fast that is associated with activation of systemic renin-angiotensin system (RAS), a decrease in plasma adiponectin (Acrp30), and insulin resistance (IR)-like conditions. Angiotensin II (Ang II) and tumor necrosis factor-alpha (TNF-α) are potential causal factors of IR, while Acrp30 may improve insulin signaling. However, the effects of fasting-induced activation of RAS on IR-like conditions in seals are not well described. To assess the effects of prolonged food deprivation on systemic and local RAS, and their potential contribution to TNF-α as they relate to an IR condition, the mRNA expressions of adipose and muscle RAS components and immuno-relevant molecules were measured along with plasma RAS components. Mean plasma renin activity and Ang II concentrations increased by 89 and 1658%, respectively, while plasma angiotensinogen (AGT) decreased by 49% over the fast, indicative of systemic RAS activation. Prolonged fasting was associated with decreases in adipose and muscle AGT mRNA expressions of 69 and 68%, respectively, corresponding with decreases in tissue protein content, suggesting suppression of local AGT production. Muscle TNF-α mRNA and protein increased by 239 and 314%, whereas those of adipose Acrp30 decreased by 32 and 98%, respectively. Collectively, this study suggests that prolonged fasting activates a systemic RAS, which contributes to an increase in muscle TNF-α and suppression of adipose Acrp30. This targeted and tissue-specific regulation of TNF-α and Acrp30 is likely coordinated to synergistically contribute to the development of an IR-like condition, independent of local RAS activity. These data enhance our understanding of the adaptive mechanisms evolved by elephant seals to tolerate potentially detrimental conditions.

Source: Journal of Experimental Biology

DOI: 10.1242/jeb.085225

Authors: Miwa Suzuki, Josá Pablo Vázquez-Medina, Jose A. Viscarra, José G. Soñanez-Organis, Daniel E. Crocker, Ortiz M. Rudy

Institutions: Nihon University, University of California, Merced, Sonoma State University

Language: English

Topic: Renin-Angiotensin System Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: University of California Merced, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute