Genetics
CETP expression reverses the obesity caused by apolipoprotein CIII overexpression in transgenic mice (Int J Obes 2007)
Original title: Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice
Since hypertriglyceridemic apolipoprotein (apo) CIII transgenic mice were previously shown to have increased whole-body metabolic rate, this study tested whether apo CIII and CETP modulate diet-induced obesity, comparing apo CIII, apo CIII/CETP double-transgenic, CETP-only, and nontransgenic mice maintained on a high-fat diet for 20 weeks after weaning. Fasting glucose was unaffected by diet or genotype, but apo CIII mice had about 35% higher fed-state glycemia and 45% lower insulin than nontransgenic mice. Apo CIII mice had significantly increased body weight, carcass lipid content (about 25% higher), visceral adipose mass (about twofold), and adipocyte size (about 25% higher) compared to CETP and nontransgenic mice. Adding CETP expression to the apo CIII background normalized subcutaneous fat and visceral adipocyte size to nontransgenic levels, and plasma leptin was lower in CETP-expressing groups. The authors conclude CETP expression reverses the adipogenic effect of elevated apo CIII, indicating a novel role for CETP in modulating adiposity.
Original abstract
Objective: We recently described that hypertriglyceridemic apolipoprotein (apo) CIII transgenic mice show increased whole body metabolic rate. In this study, we used these apo CIII-expressing mice, combined or not with the expression of the natural promoter-driven CETP gene, to test the hypothesis that both proteins modulate diet-induced obesity.
Measurements And Results: Mice expressing apo CIII, CIII/CETP, CETP and nontransgenic (NonTg) mice were maintained on a high-fat diet (14% fat by weight) during 20 weeks after weaning. At the end of this period, all groups exhibited the expected lipemic phenotype. Fasting glucose levels were neither affected by the high-fat diet nor by the distinct genotypes. However, apo CIII mice showed significantly higher glycemia ( approximately 35%) and lower insulin levels ( approximately 45%) in the fed state, compared with the NonTg mice. The apo CIII mice presented significantly increased body weight, lipid content of the carcass ( approximately 25%), visceral adipose tissue mass (about twofold) and adipocyte size ( approximately 25%) compared with the CETP and NonTg mice. The CETP expression in the apo CIII background normalized the subcutaneous adipose depot and visceral adipocyte size to the levels of NonTg mice. Plasma leptin levels were lower in CETP groups (25-50%) and higher in the apo CIII mice. Similar core body temperature in all groups and similar liver mitochondrial resting respiration rates in CIII and NonTg mice indicate no differences in basal energy expenditure rates among these mice fed a high-fat diet.
Conclusion: The elevation of plasma apo CIII levels aggravates diet-induced obesity and the expression of physiological levels of circulating CETP reverses this adipogenic effect, indicating a novel role for CETP in modulating adiposity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.