A longitudinal magnetic resonance imaging (MRI) study of differences in abdominal fat distribution between normal mice, and lean overexpressors of mitochondrial uncoupling protein‐3 (UCP‐3)

Changani, K. Kumar; Nicholson, A.; White, Alan M.; Latcham, Judy; Reid, David G.; Clapham, John C.

doi:10.1046/j.1463-1326.2003.00249.x

Cited by 29 publications

(18 citation statements)

References 24 publications

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“…TAT was calculated by adding SAT and VAT (TAT ¼ SAT þ VAT); therefore, some small intramuscular deposits of adipose tissue were not accounted for. Similar to other published reports, 5,7,18,22,25,29,[33][34][35][36][37][40][41][42][43][44][45]47,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] VAT and SAT were not further subdivided.…”

Section: Features Examinedsupporting

confidence: 79%

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging

et al. 2007

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Objective: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results. Design: Feature evaluation and test-retest reliability of softwares (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision) used in manual, semi-automated or automated segmentation of abdominal adipose tissue. Subjects: A random sample of 15 obese adults with type 2 diabetes. Measurements: Axial T1-weighted spin echo images centered at vertebral bodies of L2-L3 were acquired at 1.5 T. Five software packages were evaluated (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision), comparing manual, semi-automated and automated segmentation approaches. Images were segmented into cross-sectional area (CSA), and the areas of visceral (VAT) and subcutaneous adipose tissue (SAT). Ease of learning and use and the design of the graphical user interface (GUI) were rated. Intra-observer accuracy and agreement between the software packages were calculated using intra-class correlation. Intra-class correlation coefficient was used to obtain test-retest reliability. Results: Three of the five evaluated programs offered a semi-automated technique to segment the images based on histogram values or a user-defined threshold. One software package allowed manual delineation only. One fully automated program demonstrated the drawbacks of uncritical automated processing. The semi-automated approaches reduced variability and measurement error, and improved reproducibility. There was no significant difference in the intra-observer agreement in SAT and CSA. The VAT measurements showed significantly lower test-retest reliability. There were some differences between the software packages in qualitative aspects, such as user friendliness. Conclusion: Four out of five packages provided essentially the same results with respect to the inter-and intra-rater reproducibility. Our results using SliceOmatic, Analyze or NIHImage were comparable and could be used interchangeably. Newly developed fully automated approaches should be compared to one of the examined software packages.

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Section: Features Examinedsupporting

confidence: 79%

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging

et al. 2007

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“…After 4 and 8 months of low-fat diet, transgenic mice had lower body weights due to decreased adipose tissue mass. The effect was much less pronounced than that reported in the original transgenic model with high overexpression of UCP3 [27,35]. Differences in diet composition, age, mouse strain (C57Bl/6 vs B6D2 background for h-UCP3 mice) and UCP3 expression profile (α-skeletal actin promoter vs endogenous human regulatory sequences) may explain the discrepancies between existing UCP3-overexpressing transgenic models and h-UCP3 mice.…”

Section: Discussionmentioning

confidence: 68%

Resistance to high-fat-diet-induced obesity and sexual dimorphism in the metabolic responses of transgenic mice with moderate uncoupling protein 3 overexpression in glycolytic skeletal muscles

et al. 2007

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Aims/hypothesis Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein expressed predominantly in glycolytic skeletal muscles. Its role in vivo remains poorly understood. The aim of the present work was to produce a mouse model with moderate overproduction and proper fibre-type distribution of UCP3. Methods Transgenic mice were created with a 16 kb region encompassing the human UCP3 gene. Mitochondrial uncoupling was investigated on permeabilised muscle fibres. Changes in body weight, adiposity and glucose or insulin tolerance were assessed in mice fed chow and highfat diets. Indirect calorimetry was used to determine wholebody energy expenditure and substrate utilisation.Results Transgenic mice showed a twofold increase in UCP3 protein levels specifically in glycolytic muscles. Mitochondrial respiration revealed an increase of uncoupling in glycolytic but not in oxidative muscles. Transgenic mice gained less weight than wild-type littermates due to lower adipose tissue accretion when fed a high-fat diet. Animals showed a sexual dimorphism in metabolic responses. Female transgenic mice were more glucose-sensitive than wild-type animals, while male transgenic mice with high body weights had impaired glucose and insulin tolerance. Measurements of RQs in mice fed chow and high-fat diets suggested an impairment of metabolic flexibility in transgenic male mice. Conclusions/interpretation Our data show that physiological overproduction of UCP3 in glycolytic muscles results in mitochondrial uncoupling, resistance to high-fat dietinduced obesity and sex specificity regarding insulin sensitivity and whole-body substrate utilisation.

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“…The modest differences in body weight may also be related to a difference in the rate of turnover of AGE fat in the Reg AGE diet group, compared with the Low AGE mice. Because AGEs stimulate the production of proinflammatory cytokines, including tumor necrosis factor-␣, 46 which may promote insulin resistance, 47,48 the greater tissue AGE burden in Reg AGE mice might have contributed to the age-related impaired glucose, insulin, and fat utilization. The attenuation of these metabolic events in aged Low AGE mice in the current study was consistent with the lower AGE intake and tissue AGE deposits.…”

Section: Discussionmentioning

confidence: 99%

Reduced Oxidant Stress and Extended Lifespan in Mice Exposed to a Low Glycotoxin Diet

Cai

Zhu

et al. 2007

The American Journal of Pathology

167

176

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Aging is accompanied by increased oxidative stress (OS) and accumulation of advanced glycation end products (AGEs). AGE formation in food is temperature-regulated , and ingestion of nutrients prepared with excess heat promotes AGE formation , OS , and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (Reg AGE ) contributes to aging via an increased AGE load , which causes AGER1 dysregulation and depletion of antioxidant capacity , and that an isocaloric , but AGErestricted (by 50%) diet (Low AGE ) , would decrease these abnormalities. C57BL6 male mice with a lifelong exposure to a Low AGE diet had higher than baseline levels of tissue AGER1 and glutathione/ oxidized glutathione and reduced plasma 8-isoprostanes and tissue RAGE and p66 shc levels compared with mice pair-fed the regular (Reg AGE ) diet. This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance , albuminuria , and glomerulosclerosis. Moreover , lifespan was extended in Low AGE mice , compared with Reg AGE mice. Thus , OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants that exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved these innate defenses , resulting in decreased tissue damage and a longer lifespan in mice. Environmental and genetic factors including elevated oxidant stress (OS), cumulative DNA damage, altered gene expression, telomere shortening, and energy utilization are among the postulated mechanisms of senescence and aging in organisms from yeast to mammals.

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A longitudinal magnetic resonance imaging (MRI) study of differences in abdominal fat distribution between normal mice, and lean overexpressors of mitochondrial uncoupling protein‐3 (UCP‐3)

Abstract: MRI provides an excellent approach to comparative studies of fat distribution in animal models of energy expenditure such as the UCP-3tg mouse.

Cited by 29 publications

References 24 publications

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging

Resistance to high-fat-diet-induced obesity and sexual dimorphism in the metabolic responses of transgenic mice with moderate uncoupling protein 3 overexpression in glycolytic skeletal muscles

Reduced Oxidant Stress and Extended Lifespan in Mice Exposed to a Low Glycotoxin Diet

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