Overindulgence and metabolic syndrome: is FoxO1 a missing link?
Excessive production of triglyceride-rich VLDL, which can result from dietary overindulgence, underlies metabolic syndrome--a combination of disorders including high blood pressure, obesity, high triglyceride, and insulin resistance--and places individuals at increased risk of developing cardiovascular disease and type 2 diabetes. However, the link between VLDL overproduction and insulin resistance has remained unclear. VLDL assembly in the liver is catalyzed by microsomal triglyceride transfer protein (MTP). In this issue of the JCI, Kamagate et al. investigate the events controlling hepatic MTP expression and VLDL production and secretion (see the related article beginning on page 2347). They demonstrate that MTP is a target of the transcription factor FoxO1 and that excessive VLDL production associated with insulin resistance is caused by the inability of insulin to regulate FoxO1 transcriptional activation of MTP.
Sparks
Janet D
JD
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. janet_sparks@urmc.rochester.edu
Sparks
Charles E
CE
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D002352:Carrier Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein