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      Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging

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          Abstract

          Background

          Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy.

          Methods

          We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects.

          Results

          Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects.

          Conclusion

          Semi-automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings.

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          Most cited references20

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          PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy.

          Autosomal dominant familial partial lipodystrophy (FPLD) due to mutant LMNA encoding nuclear lamin A/C is characterized by adipose tissue repartitioning together with multiple metabolic disturbances, including insulin resistance and dyslipidemia. There is emerging evidence that some rare mutations in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), encoded by PPARG, might be associated with human lipodystrophy. We report a three-generation Canadian kindred ascertained based upon partial lipodystrophy, with a normal LMNA gene sequence. Candidate gene sequencing showed that all four affected subjects were heterozygous for a novel T-->A mutation at PPARG nucleotide 1164 in exon 5 that predicted substitution of phenylalanine at codon 388 by leucine (F388L). The mutation was absent from normal family members and normal unrelated subjects, and altered a highly conserved residue within helix 8 of the predicted ligand-binding pocket of PPAR-gamma. The mutant receptor had significantly decreased basal transcriptional activity and impaired stimulation by a synthetic ligand. The germline transmission of a transactivation-deficient mutation in PPARG suggests that autosomal dominant partial lipodystrophy is genetically heterogeneous. Our findings are consistent with the idea that mutant PPARG can underlie the partial lipodystrophy phenotype.
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            Regional adiposity and insulin resistance.

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              Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers.

              The evaluation of adipose tissue distribution has become an essential component of investigations on the complications of obesity. However, a major limitation is lack of methodology for accurate estimation of adipose tissue mass in the different regions of the body. Therefore, we have tested the accuracy and precision of magnetic resonance imaging (MRI) as a method to measure adipose tissue mass in regions of the body not accessible with standard anthropometric methods. The mass of subcutaneous and intraabdominal adipose tissue estimated by MRI was compared with that obtained by direct weighing of the same adipose tissue compartments after dissection in human cadavers. MRI was performed on three unembalmed cadavers (two males, one female) who were subsequently dissected to isolate intraperitoneal, retroperitoneal, and subcutaneous adipose tissues. These same components were delineated by MRI. The results of the two methods were highly congruent. For the various compartments, the mean of the difference between the two methods was only 0.076 kg (95% confidence interval + 0.005 kg and + 0.147 kg). The "limits of agreement" between the two techniques were -0.066 kg and +0.218 kg. Multiple repeated estimates of mass of adipose tissue compartments were made to determine reproducibility of the MRI measurement; the coefficient of variation for repeated measures was below 14%. The results of this study show that MRI is an accurate and precise technique to evaluate adipose tissue mass in subcutaneous and intraabdominal compartments. Furthermore, MRI was found to be a valid method to separately evaluate the mass of intraabdominal subcompartments of intraperitoneal and retroperitoneal adipose tissue.
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                Author and article information

                Journal
                BMC Med Imaging
                BMC Medical Imaging
                BioMed Central (London )
                1471-2342
                2007
                12 March 2007
                : 7
                : 3
                Affiliations
                [1 ]Vascular Biology Research Group, Robarts Research Institute, London, Ontario, N6A 5K8, Canada
                [2 ]Imaging Research Laboratories, Robarts Research Institute, London, Ontario, N6A 5K8, Canada
                [3 ]Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, N6A 5A5, Canada
                [4 ]Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 100 Perth Drive, Room 406, London, Ontario, N6A 5K8, Canada
                Article
                1471-2342-7-3
                10.1186/1471-2342-7-3
                1832180
                17352814
                aa5d83be-cad4-470a-9322-f7d2a4e17e64
                Copyright © 2007 Al-Attar et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 November 2006
                : 12 March 2007
                Categories
                Research Article

                Radiology & Imaging
                Radiology & Imaging

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