Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in adiposity and insulin resistance.

Abstract

Apolipoprotein A-II (apoA-II) is the second most abundant protein in HDLs. Genetic studies in humans have provided evidence of linkage of the apoA-II gene locus to plasma free fatty acid (FFA) levels and to type 2 diabetes, and transgenic mice overexpressing mouse apoA-II have elevated levels of both FFA and triglycerides. We now show that apoA-II promotes insulin resistance and has diverse effects on fat homeostasis. ApoA-II transgenic mice have increased adipose mass and higher plasma leptin levels than C57BL/6J control mice. Fasting glucose levels were similar between apoA-II transgenic and control mice, but plasma insulin levels were elevated approximately twofold in the apoA-II transgenic mice. Compared with control mice, apoA-II transgenic mice exhibited a delay in plasma clearance of a glucose bolus. Adipose tissue isolated from fasted apoA-II transgenic mice exhibited a 50% decrease in triglyceride hydrolysis compared with adipose tissue from control mice. This is consistent with a normal response of adipose tissue to the increased insulin levels in the apoA-II transgenic mice and may partially explain the increased fat deposition. Skeletal muscle isolated from fasted apoA-II transgenic mice exhibited reduced uptake of 2-deoxyglucose compared with muscles isolated from control mice. Our observations indicate that a primary disturbance in lipoprotein metabolism can result in several traits associated with insulin resistance, consistent with the hypothesis that insulin resistance and type 2 diabetes can, under certain circumstances, be related primarily to altered lipid metabolism rather than glucose metabolism.

• Authors: L W Castellani, A M Goto, A J Lusis
• Journal: Diabetes (Diabetes) Vol. 50 Issue 3 Pg. 643-51 (Mar 2001) ISSN: 0012-1797 [Print] United States
• PMID: 11246886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoprotein A-II
• Blood Glucose
• Lipoproteins, HDL
• Triglycerides
• Deoxyglucose

Topics

• Adipose Tissue (anatomy & histology, metabolism)
• Animals
• Apolipoprotein A-II (genetics, physiology)
• Blood Glucose (metabolism)
• Deoxyglucose (pharmacokinetics)
• Fasting (metabolism)
• Hydrolysis
• Insulin Resistance (physiology)
• Lipoproteins, HDL (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic (genetics)
• Muscle, Skeletal (metabolism)
• Reference Values
• Triglycerides (metabolism)