Insulin resistance and the
metabolic syndrome are associated with fasting and postprandial
dyslipidemia. This involves the hepatic and intestinal overproduction of
very low density lipoproteins (VLDL) and
chylomicron particles, respectively, which give rise to atherogenic remnants upon lipolysis in the circulation. Recently, the
insulin secretagogue glucagon-like peptide-1 (GLP-1) has received attention not only as an anti-diabetic
therapy for regulating glycaemia, but also as a regulator of
lipid and
lipoprotein metabolism. In fact, agents that raise endogenous bioactive levels of
GLP-1 (
dipeptidyl peptidase 4 inhibitors) and agents that directly stimulate
GLP-1 receptors (
GLP-1 receptor agonists) have been assessed in both preclinical and clinical trials for their ability to modulate plasma
lipid parameters. Here we describe current evidence supporting a role for
GLP-1 in preventing elevated intestinal
chylomicron output and postprandial
hypertriglyceridemia--an independent predictor of cardiovascular risk. Furthermore, we examine a role for
GLP-1 in regulating fasting hepatic VLDL production and hindering the development of a potentially devastating comorbidity, hepatic steatosis. Possible mechanisms of action of
GLP-1 are discussed including a reduction in intestinal absorption of dietary
lipid and enhanced hepatic
fatty acid oxidation or autophagy. Finally, we discuss the current controversy over whether these effects could occur via direct receptor stimulation or alternative, indirect pathways. We conclude that GLP- 1-based
therapies appear promising in the management of diabetic
dyslipidemia, and further studies are warranted to elucidate their mechanisms of action in both the intestine and liver.