Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice
article
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. © 2005 by the American Diabetes Association. Chemicals / CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; lipoprotein lipase, 83137-80-8, 9004-02-8; Apolipoprotein C-III; Apolipoproteins C; Blood Glucose; Dietary Fats; Fatty Acids; Triglycerides
Topics
Biomedical Researchalbuminapolipoprotein C3fatty acidglucoseinsulinlipoprotein lipasetriacylglycerolanimal cellanimal experimentanimal tissuebody fatbody massbody weightcontrolled studydietenzyme activityfatty acid transportgluconeogenesisglucose blood levelglucose clamp techniqueinsulin resistanceinsulin sensitivitylipid dietmousenonhumanprotein deficiencytriacylglycerol blood levelwild typeAdipose TissueAnimalsApolipoprotein C-IIIApolipoproteins CBlood GlucoseDietary FatsFatty AcidsFemaleInsulin ResistanceMaleMiceMice, Inbred C57BLMice, KnockoutObesityTime FactorsTriglycerides
TNO Identifier
238358
ISSN
00121797
Source
Diabetes, 54(3), pp. 664-671.
Pages
664-671
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