title: Activation of systemic, but not local, renin-angiotensin system is associated with upregulation of TNF-α during prolonged fasting in northern elephant seal pups.
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.
authors.affiliation: Department of Molecular and Cellular Biology, University of California Merced, Merced, CA 95343, USA. suzuki.miwa@nihon-u.ac.jp
authors.forename: Miwa
authors.initials: M
authors.lastname: Suzuki
authors.forename: José Pablo
authors.initials: JP
authors.lastname: Vázquez-Medina
authors.forename: Jose A
authors.initials: JA
authors.lastname: Viscarra
authors.forename: José G
authors.initials: JG
authors.lastname: Soñanez-Organis
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Crocker
authors.forename: Rudy M
authors.initials: RM
authors.lastname: Ortiz
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002140:California; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D007333:Insulin Resistance; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System; D046048:Seals, Earless / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D018932:Chemokine CCL2; D018076:DNA, Complementary; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: adiponectin; food deprivation; insulin resistance; obesity; renin–angiotensin system; tumor necrosis factor-alpha