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Objective:The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage.Methods and results:We identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. We evaluated the role of wild-type (wt) and mutant UCP3 proteins in palmitate oxidation and in triglyceride storage in human embryonic kidney cells (HEK293). Palmitate oxidation was ∼60% lower (P<0.05; P<0.01) and triglyceride storage was higher in HEK293 cells expressing the four UCP3 mutants than in cells expressing wt UCP3. Moreover, mutants V56M and Q252X exerted a dominant-negative effect on wt protein activity (P<0.01 and P<0.05, respectively). Telmisartan, an angiotensin II receptor antagonist used in the management of hypertension, significantly (P<0.05) increased palmitate oxidation in HEK293 cells expressing wt and mutant proteins (P<0.05; P<0.01), including the dominant-negative mutants.Conclusions:These data indicate that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Our results also suggest that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants. [ABSTRACT FROM AUTHOR]

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6±2.6 years; range 6–14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl−1, fasting triglyceride concentration >100 mg dl−1, fasting high-density lipoprotein cholesterol concentration <50 mg dl−1 for females or <45 mg dl−1 for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima–media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima–media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83±1.86 mm2 [mean±s.d.] compared with the control group: 7.77±1.72 mm2, P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.Journal of Human Hypertension (2008) 22, 83–88; doi:10.1038/sj.jhh.1002289; published online 11 October 2007 [ABSTRACT FROM AUTHOR]