Adiponectin Diminishes Organ-Specific Microvascular Endothelial Cell Activation Associated With Sepsis

Abstract

Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in mice with endotoxemic challenge and after cecal ligation and puncture compared with healthy control mice. Quantitative reverse transcriptase-polymerase chain reaction for adiponectin reveals a pattern of response that is both model- and organ-specific. When challenged with sepsis, adiponectin deficiency results in increased expression of endothelial adhesion and coagulation molecules in the lung, liver, and kidney as quantified by reverse transcriptase-polymerase chain reaction, increased macrophage and neutrophil infiltration by immunohistochemistry, and vascular leakage in the liver and kidney. Adiponectin-deficient mice have reduced survival following cecal ligation and puncture and increased blood levels of interleukin 6, soluble vascular endothelial growth factor receptor 1, and soluble endothelial adhesion molecules E-selectin and intercellular adhesion molecule 1. Finally, ADPNKO promoted end-organ injury in the liver and kidney, whereas the lungs were not affected. These data suggest a protective role of adiponectin in diminishing microvascular organ-specific endothelial cell activation during sepsis.

Visfatin Promotes Foam Cell Formation by Dysregulating Cd36, Sra, Abca1, and Abcg1 Expression in RAW264.7 Macrophages

“…This observation suggested dysregulation of adipokines may play an etiological role in the development of endotoxin shock in obese patients. Adiponectin, downregulation in obese status, reduced organ-specific microvascular endothelial cell activation during sepsis (46). Leptin, upregulation in obese status, played a crucial role in nonalcoholic steatohepatitis progression via enhanced responsivity to endotoxin (47).…”

Adiponectin as a Predictor for the Severity of Sepsis in ICU Patients

“…So the authors suggested that low adiponectin may guide to a high risk for sepsis-related complications [33]. Van Meurs and his colleagues induced experimental sepsis in mice, circulating adiponectin is reduced in mice with endotoxemic challenge compared with healthy control mice [47].…”

Plasma Adiponectin, Clinical Factors, and Patient Outcomes during the Acute Respiratory Distress Syndrome

“…Adiponectin (APN) is a highly abundant circulating hormone with pleotrophic effects upon diverse pulmonary cell types [1]–[4] including alveolar macrophages, epithelium, and vascular endothelium [3], [5], [6]. Though principally derived from adipocytes, circulating APN levels are paradoxically increased in lean individuals and decreased in subjects with higher body mass indexes [7].…”

“…Though principally derived from adipocytes, circulating APN levels are paradoxically increased in lean individuals and decreased in subjects with higher body mass indexes [7]. In the lung, APN has been shown to have important anti-inflammatory and vascular protective actions, prompting pre-clinical studies examining the role of APN in the pathogenesis of pulmonary disorders including acute respiratory distress syndrome (ARDS) [2]–[4], [8] …”

“…Although the role of circulating APN in human ARDS has not yet been investigated, animal studies suggest a causal link between hypoadiponectemia and ARDS pathogenesis. For example, APN-deficient mice have a markedly increased susceptibility to developing acute lung injury (the murine equivalent of ARDS) [2], [4], [6], [8] and this susceptibility is attenuated following APN replacement [3]. Further, mice deficient in APN are prone to developing pulmonary vascular abnormalities including elevated pulmonary artery pressures [5], a hemodynamic alteration associated with increased mortality among patients with ARDS [10].…”