Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice.
Our aim was to study whether the absence of apolipoprotein (apo) C3, a strong inhibitor of lipoprotein lipase (LPL), accelerates the development of obesity and consequently insulin resistance. Apoc3(-/-) mice and wild-type littermates were fed a high-fat (46 energy %) diet for 20 weeks. After 20 weeks of high-fat feeding, apoc3(-/-) mice showed decreased plasma triglyceride levels (0.11 +/- 0.02 vs. 0.29 +/- 0.04 mmol, P < 0.05) and were more obese (42.8 +/- 3.2 vs. 35.2 +/- 3.3 g; P < 0.05) compared with wild-type littermates. This increase in body weight was entirely explained by increased body lipid mass (16.2 +/- 5.9 vs. 10.0 +/- 1.8 g; P < 0.05). LPL-dependent uptake of triglyceride-derived fatty acids by adipose tissue was significantly higher in apoc3(-/-) mice. LPL-independent uptake of albumin-bound fatty acids did not differ. It is interesting that whole-body insulin sensitivity using hyperinsulinemic-euglycemic clamps was decreased by 43% and that suppression of endogenous glucose production was decreased by 25% in apoc3(-/-) mice compared with control mice. Absence of apoC3, the natural LPL inhibitor, enhances fatty acid uptake from plasma triglycerides in adipose tissue, which leads to higher susceptibility to diet-induced obesity followed by more severe development of insulin resistance. Therefore, apoC3 is a potential target for treatment of obesity and insulin resistance.
Duivenvoorden
Ilse
I
TNO Prevention and Health, Gambius Laboratory, Leiden, Netherlands.
Teusink
Bas
B
Rensen
Patrick C
PC
Romijn
Johannes A
JA
Havekes
Louis M
LM
Voshol
Peter J
PJ
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D014280:Triglycerides