Insulin deficiency in diabetic mice caused hypertriglyceridemia by decreasing peripheral lipolysis and postprandial triglyceride clearance, rather than increasing hepatic triglyceride production.
Does insulin deficiency cause hypertriglyceridemia via increased hepatic lipogenesis or decreased peripheral lipolysis in diabetic mice?
In diabetic mice, hypertriglyceridemia is driven by decreased peripheral lipolysis rather than increased hepatic triglyceride production.
OBJECTIVE: Diabetic hypertriglyceridemia is thought to be primarily driven by increased hepatic de novo lipogenesis. However, experiments in animal models indicated that insulin deficiency should decrease hepatic de novo lipogenesis and reduce plasma triglyceride levels. APPROACH AND RESULTS: To address the discrepancy between human data and genetically altered mouse models, we investigated whether insulin-deficient diabetic mice had triglyceride changes that resemble those in diabetic humans. Streptozotocin-induced insulin deficiency increased plasma triglyceride levels in mice. Contrary to the mouse models with impaired hepatic insulin receptor signaling, insulin deficiency did not reduce hepatic triglyceride secretion and de novo lipogenesis-related gene expression. Diabetic mice had a marked decrease in postprandial triglycerides clearance, which was associated with decreased lipoprotein lipase and peroxisome proliferator-activated receptor α mRNA levels in peripheral tissues and decreased lipoprotein lipase activity in skeletal muscle, heart, and brown adipose tissue. Diabetic heterozygous lipoprotein lipase knockout mice had markedly elevated fasting plasma triglyceride levels and prolonged postprandial triglycerides clearance. CONCLUSIONS: Insulin deficiency causes hypertriglyceridemia by decreasing peripheral lipolysis and not by an increase in hepatic triglycerides production and secretion.
Willecke et al. (2014) studied Diabetic hypertriglyceridemia. Streptozotocin-induced insulin deficiency was evaluated on Plasma triglyceride levels and clearance. Insulin deficiency in diabetic mice caused hypertriglyceridemia by decreasing peripheral lipolysis and postprandial triglyceride clearance, rather than increasing hepatic triglyceride production.
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