Cardiovascular significance of adipose-derived adiponectin and liver-derived xanthine oxidoreductase in metabolic syndrome.

Abstract

Visceral fat-based metabolic syndrome has a strong impact on atherosclerotic cardiovascular disease (CVD), clustering diabetes, dyslipidemia, hypertension, hyperuricemia, and non-alcoholic fatty liver disease (NAFLD). Adiponectin, a protein specifically secreted by adipocytes, circulates abundantly in the human bloodstream, but its concentration decreases under pathological conditions such as visceral fat accumulation. Extensive clinical evidence has demonstrated that hypoadiponectinemia is associated with the development of CVD and chronic organ diseases. Although several binding partners of adiponectin, such as AdipoR1/2, have been identified, how adiponectin exerts its multiple beneficial effects on various organs remains to be fully elucidated. Recent progress in adiponectin research has revealed that adiponectin accumulates on cardiovascular tissues by binding to a unique glycosylphosphatidylinositol-anchored T-cadherin. The adiponectin/T-cadherin complex enhances exosome biogenesis and secretion, which may contribute to the maintenance of cellular homeostasis and tissue regeneration, particularly in the vasculature. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catabolizes hypoxanthine and xanthine to uric acid. XOR produces reactive oxygen species in the reaction process, suggesting that XOR is involved in the pathological mechanism underlying CVD progression. Recent findings from clinical and laboratory studies have shown strong positive correlations between plasma XOR activity and liver enzymes. Furthermore, especially in NAFLD conditions, excessive hepatic XOR leaked into the bloodstream accelerates purine catabolism in the circulation, using hypoxanthine secreted from vascular endothelial cells and adipocytes, which can promote vascular remodeling. In this review, we focused on the cardiovascular significance of adipose-derived adiponectin and liver-derived XOR in the development of CVD associated with metabolic syndrome.

• Authors: Yuya Fujishima, Shunbun Kita, Hitoshi Nishizawa, Norikazu Maeda, Iichiro Shimomura
• Journal: Endocrine journal (Endocr J) Vol. 70 Issue 7 Pg. 663-675 (Jul 28 2023) ISSN: 1348-4540 [Electronic] Japan
• PMID: 37316258 (Publication Type: Review, Journal Article)

Chemical References

• Adiponectin
• Xanthine Dehydrogenase
• Hypoxanthines

Topics

• Humans
• Metabolic Syndrome
• Adiponectin
• Xanthine Dehydrogenase
• Non-alcoholic Fatty Liver Disease
• Endothelial Cells (metabolism)
• Obesity
• Hypertension
• Hypoxanthines