Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice

• Published in: International Journal of Obesity 2007-10, Vol.31 (10), p.1586-1595
• Main Authors: Salerno, A.G, Silva, T.R, Amaral, M.E.C, Alberici, L.C, Bonfleur, M.L, Patricio, P.R, Francesconi, E.P.M.S, Grassi-Kassisse, D.M, Vercesi, A.E, Boschero, A.C
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipose tissue; animal models; Animals; Apolipoprotein C-III - physiology; Apolipoproteins; Atherosclerosis; Biological and medical sciences; blood chemistry; blood glucose; blood proteins; Body Composition - physiology; Body fat; Body temperature; Body weight; Body Weight - physiology; cell respiration; Cholesterol; Cholesterol Ester Transfer Proteins - physiology; cholesteryl ester transfer protein; Diet; Disorders of blood lipids. Hyperlipoproteinemia; Epidemiology; Fasting - blood; Fasting - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene expression; genes; Genetic aspects; Genotypes; Health aspects; Health Promotion and Disease Prevention; High density lipoprotein; high fat diet; Hypertriglyceridemia - blood; Hypertriglyceridemia - metabolism; Hypotheses; Insulin; Internal Medicine; leptin; Leptin - metabolism; Lipoproteins; Liver; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; molecular sequence data; Obesity; original-article; phenotype; Physiology; Plasma; postprandial state; promoter regions; protein synthesis; Proteins; Public Health; Respiration; Risk factors; Transgenic animals; Vertebrates: anatomy and physiology, studies on body, several organs or systems; visceral fat; Weaning
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803646

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.