Reduction of Insulin Signaling Upregulates Angiopoietin-like Protein 4 Through Elevated Free Fatty Acids in Diabetic Mice

Abstract

These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

Dietary modulation of plasma angiopoietin-like protein 4 concentrations in healthy volunteers and in patients with type 2 diabetes

“…Because insulin caused a decrease in plasma NEFA concentrations in both studies, it is possible that the effect of insulin on plasma ANGPTL4 is mediated by a decrease in NEFAs. In addition, evidence indicates that insulin can suppress ANGPTL4 production independent of NEFAs (13,24). We observed increased NEFA and ANGPTL4 concentrations after the VLCD (study B) and HFED (study C) and unchanged and increased insulin concentrations, respectively.…”

“…Limited evidence indicates that fasting may increase plasma ANGPTL4 concentrations (11). In addition to its functions in normal physiology, ANGPTL4 also seems to play a relevant role in the metabolic syndrome and type 2 diabetes mellitus, both of which are associated with dyslipidemia, including hypertriglyceridemia and high concentrations of NEFAs (12)(13)(14). In db/db diabetic mice, overexpression of ANGPTL4 induces hypertriglyceridemia and hepatic steatosis while at the same time reduces blood glucose and hepatic glucose output (14).…”

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

“…Treatment with the synthetic glucocorticoid dexamethasone increased ANGPTL4 expression in vitro in HepG2 cells [19] and in primary cultures of hepatocytes and adipocytes, as well as in the livers and white adipose tissue of mice in vivo [8]. Moreover, it has been observed that under hyperinsulinemic conditions, such as hyperinsulinemic clamp in humans [19] and insulin treated mice [42], the expression and concentration of ANGPTL4 is reduced. These observations are interesting because increased fetal adrenal cortisol and decreased fetal insulin concentrations are two of the main signals that promote the mobilization of fatty acids from fetal fat depots and their subsequent oxidation in neonatal tissues with the onset of labor [21], [23].…”

Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin

“…Previous studies have shown that serum ANGPTL4 levels and the expression of ANGPTL4 are inversely correlated with insulin sensitivity (21)(22)(23). In 3T3-L1 adipocytes, insulin suppresses Angptl4 gene expression ( 24,25 ).…”