Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic deterioration in mice

Abstract

Acute systemic removal of APN results in a much more negative metabolic phenotype compared with congenital knockout of Adipoq. Specifically, our data demonstrate that acute depletion of APN is especially detrimental to lipid homeostasis, both under basal and insulinopenic conditions. This suggests that compensatory mechanisms exist in congenital knockout mice that offset some of the metabolic actions covered by APN.

Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication

“…Ceramide degradation is intimately connected to adiponectin signaling, as the engagement of AdipoR1 and Adi-poR2 is associated with increased ceramidase activity, which may stem from the receptors themselves (117,(321)(322)(323)(324). Adiponectin-deficient mice display not only impaired glucose tolerance and insulin sensitivity, but also increased ceramide and decreased sphingosine and S1P levels in WAT and liver as well as exacerbated responses upon experimental induction of -cell and cardiac muscle cell death (117,321). Treatment with adiponectin or overexpression of it decreases tissue ceramide levels, normalizes glucose homeostasis upon high-fat feeding, and restrains -cell and cardiac muscle cell death, likely through induction of ceramide degradation and S1P production (321).…”

Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome

“…Furthermore, SNPs' small effects on plasma adiponectin levels might be compensated for during life-long periods in human subjects. Indeed, it was reported that the acute depletion of adiponectin resulted in more severe systemic insulin resistance and hyperlipidemia than in mice with congenital loss of adiponectin (102).…”

The Role of Ceramides in Diabetes and Cardiovascular Disease Regulation of Ceramides by Adipokines

“…Conversely, elimination of adiponectin production from adipocytes led to increased ceramide deposition in the liver ( 108 ). Specifically, ceramide species C16:0, C18:0, C24:0, and C24:1 were elevated, while ceramide breakdown products sphingosine and sphingosine-1-phosphate (S1P) were lowered ( 154 ). Blocking ceramide production with SPT inhibitor myriocin in DIO mice led to increased levels of circulating high molecular weight adiponectin ( 59 ).…”