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      Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice

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          Abstract

          Objectives

          Obesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice.

          Methods

          Different lean and obese mouse models (C57BL/6, B6.V-Lep ob, NZO) were used to determine the most adequate scanning parameters for the detection of the different fat depots. The data were compared with those obtained after preparation and weighing the fat depots. Liver fat content was determined by biochemical analysis.

          Results

          The correlations between weights of fat tissues on scale and weights determined by CT were significant for subcutaneous (r 2 = 0.995), visceral (r 2 = 0.990) and total white adipose tissue (r 2 = 0.992). Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5 correlated with whole-body fat distribution allowing experimenters to reduce scanning time and animal exposure to radiation and anesthesia. Test-retest reliability and measurements conducted by different experimenters showed a high reproducibility in the obtained results. Intrahepatic fat content estimated by CT was linearly related to biochemical analysis (r 2 = 0.915). Furthermore, brown fat mass correlated well with weighted brown fat depots (r 2 = 0.952). In addition, short-term cold-expose (4°C, 4 hours) led to alterations in brown adipose tissue attributed to a reduction in triglyceride content that can be visualized as an increase in Hounsfield units by CT imaging.

          Conclusion

          The 3D imaging of fat by CT provides reliable results in the quantification of total, visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive method allows the conduction of longitudinal studies of obesity in mice and therefore enables experimenters to investigate the onset of complex diseases such as diabetes and obesity.

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          Most cited references30

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          Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans.

          Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.
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            Non alcoholic fatty liver disease and metabolic syndrome.

            Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seems to have common pathophysiological mechanisms, with focus on insulin resistance as a key factor. This review summarizes the current knowledge on the epidemiology, pathophysiology and diagnosis of both NAFLD and metabolic syndrome and the findings that strongly support the association of nonalcoholic fatty liver disease as a possible component in the cluster of metabolic syndrome.
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              Overweight and obesity: prevalence, consequences, and causes of a growing public health problem.

              This paper provides an overview of the evidence on the current epidemic of obesity in the United States. The prevalence of overweight and obesity now exceeds 60% among US adults, and the rate is rapidly increasing among children and adolescents. Dismal medical, social, and economic consequences are already apparent and likely to worsen without multipronged intervention. Increased rates of hypertension, diabetes, and dyslipidemia, among other medical conditions, threaten to shorten the longevity of the American populace by as much as 5 years. The incidence of depression is increasing and experts suggest this is linked with the increased prevalence of obesity. The cost of obesity-related medical care has increased astronomically since 1987, in addition to lost productivity and income. Novel multidisciplinary, preventive, and therapeutic approaches, and social changes are needed that address the complex interplay of biologic, genetic, and social factors that have created the current obesity epidemic.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                16 May 2012
                : 7
                : 5
                : e37026
                Affiliations
                [1]Department of Experimental Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
                University of Tübingen, Germany
                Author notes

                Conceived and designed the experiments: SS PW AS. Performed the experiments: ML DH NN. Analyzed the data: ML DH NN. Contributed reagents/materials/analysis tools: SS PW AS. Wrote the paper: ML AS.

                Article
                PONE-D-12-00945
                10.1371/journal.pone.0037026
                3353985
                22615880
                c26470de-fdb0-4a88-9131-fcfc96a79a6f
                Lubura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 4 January 2012
                : 16 April 2012
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Diagnostic Medicine
                Endocrinology
                Diabetic Endocrinology
                Metabolic Disorders
                Nutrition
                Obesity
                Radiology
                Diagnostic Radiology
                Computed Tomography

                Uncategorized
                Uncategorized

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