Body Metabolism: More to Life than Fat
Friday 7 May 2010
Room A7 10:30-12:30 Moderators: Claude B. Sirlin and Kristen L. Zakian

10:30 744. 

Evaluation of Liver Regeneration in Human After Portal Vein Embolization and Partial Hepatectomy Using in Vivo 1H Decoupled - 31P Magnetic Resonance Spectroscopy Imaging
Jing Qi1, Amita Shukla-Dave, Yuman Fong2, Mithat Gönen3, Lawrence H. Schwartz4, William M. Jarnagin2, Jason A. Koutcher, Kristen L. Zakian1
Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; 2Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; 3Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; 4Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States

To compare the metabolic feature of hepatic regeneration stimulated by portal vein embolization (PVE) and partial hepatectomy (PH), liver 1H-decoupled 31P-MRSI data acquired from 8 healthy subjects, 6 patients at 48 hours following PVE and 4 patients at 48 hours following PH were analyzed. PH showed similar PME/NTP value as PVE, but significantly higher than control group. PH had significantly elevated PME/PDE, PE/NTP and PE/PC ratios but lower PC/NTP ratio compared to PVE and control subjects. The biochemical difference at 48 hours following PH and PVE indicated that hepatic regeneration process after PVE is not as strong as PH.

10:42 745. 

In Vivo Hepatic Localized Proton Magnetic Resonance Spectroscopy at 7T in a Glycogen Storage Disease Mouse Model
Nirilanto Ramamonjisoa1, Hélène Ratiney1, Fabienne Rajas2, Elodie Mutel2, Frank Pilleul1,3, Olivier Beuf1, Sophie Cavassila1
Université de Lyon, CREATIS-LRMN; CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France; 2Inserm U855; Université Lyon1, Faculté de Médecine Laennec, Lyon, France; 3Imagerie Digestive - CHU, Hospices Civils de Lyon, Lyon, France

In vivo 1H magnetic resonance spectroscopy (MRS) was used to evaluate the hepatic steatosis in a mouse model of GSD1a under two different diets, a standard- and a high fat diet. Accumulation of hepatic fat and fat composition within the liver were assessed. The estimated MRS profiles for both groups (Figure 2) showed significant differences for the lipid methyl resonances at 0.9ppm. Both estimated levels of the methylene resonances (1.3ppm) were significantly higher than the estimates obtained for control mice fed on standard diet. Based on MR imaging observations, 90% of the mice fed on high-fat diet exhibited adenomas in the liver while none fed on standard diet. These measurements will give insight into the understanding of the onset and progression of adenomas in a mouse model of GSD1a under different diets

10:54 746. 

Regional Variability in Triglyceride Composition of Adipose Tissue Measured by 1H MRS
Gavin Hamilton1, Michael S. Middleton1, Takeshi Yokoo1, Mark Bydder1, Michael E. Schroeder1, Claude B. Sirlin1
Department of Radiology, University of California, San Diego, San Diego, CA, United States

The multi-peak structure of the fat 1H MR spectrum allows non-invasive estimation of the triglyceride composition of adipose tissue.  The study compares variability in triglyceride composition of two locations in subcutaneous adipose tissue to the variability seen between subcutaneous and visceral adipose tissue.  We see agreement in triglyceride composition in different locations in subcutaneous adipose tissue, but triglyceride composition of visceral tissue varies compared to that of subcutaneous tissue.

11:06 747.  

Liver Fat Is More Saturated Than Adipose Fat as Determined by Long TE 1H-MRS
Jesper Lundbom1, Antti Hakkarainen1, Sanni Söderlund2, Jukka Westerbacka2, Nina Lundbom1, Marja-Riitta Taskinen2
HUS Medical Imaging Centre, University of Helsinki, Helsinki, Finland; 2Department of Medicine, University of Helsinki, Finland

We used long TE 1H-MRS to show that liver fat is more saturated than subcutaneous and intra-abdominal adipose tissue.

11:18 748.

In Vivo Identification of a Molecular Marker for Brown Adipose Tissue in NMR Spectra of Large Volumes
Rosa Tamara Branca1, Warren Sloan Warren2
1Chemistry, Duke University, Durham, NC, United States; 2Chemistry, Duke University, Durham, NC, United States

A molecular signature of brown adipose tissue is found in the iZQC spectrum of mice. More specifically the iZQC resonance frequency line between methylene protons (-CH2-) at 1.3ppm and water, at cellular length scales, seems to be characteristic of the only BAT tissue. This method is applied in vivo to screen normal and obesity mouse models, and to track the BAT response to adrenergic stimulation and cold exposure.

11:30 749

Characterization of Brown Adipose Tissue in Mice with IDEAL Fat-Water MRI
Houchun Harry Hu1, Daniel Larry Smith, Jr. 2, Michael I. Goran3, Tim R. Nagy2, Krishna S. Nayak1
1Electrical Engineering, University of Southern California, Los Angeles, CA, United States; 2Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States; 3Preventive Medicine, Pediatrics, Physiology & Biophysics, University of Southern California, Los Angeles, CA, United States

The fat fraction from IDEAL-MRI is used to non-invasively characterize brown adipose tissue (BAT) in mice.  We first demonstrate the ability to identify various BAT depots with IDEAL.  We then demonstrate with IDEAL differences in BAT between mice that were housed at 19°C and 25.5°C for three consecutive weeks.  The interscapular BAT fat fractions in the colder animals were (35.2–48.6%), in contrast to the warmer animals (48.4–60.9%), p<0.01.  The two groups exhibited similar gains in body weight, despite a significant 29% greater food intake by the 19°C animals.  These findings support BAT’s involvement in thermogenesis and lipid metabolism.

11:42 750

Pancreatic and Hepatic Fat and Associated Metabolic Complications in Overweight Youth
Catriona A. Syme1, Greg D. Wells1,2, Garry Detzler1, Hai-Ling Margaret Cheng1,2, Mike D. Noseworthy3,4, Timo Schirmer5, Brian W. McCrindle2,6, Jill Hamilton, 2,7

1Physiology & Experimental Medicine, The Hospital for Sick Children, Toronto, ON, Canada; 2University of Toronto, Toronto, ON, Canada; 3Electrical and Computer Engineering, McMaster University, Hamilton, ON, Canada; 4Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada; 5Applied Science Laboratory, GE Healthcare, Munich, Germany; 6Cardiology, The Hospital for Sick Children, Toronto, ON, Canada; 7Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada

In overweight youth, pancreatic and hepatic fat (PF and HF) were estimated from in- and out-of-phase MRI, and associations with metabolic parameters were assessed. Both showed positive correlations with triglycerides and insulin resistance and secretion. HF did not correlate with liver enzymes, suggesting its early accumulation may influence glucose metabolism before elevation of hepatic transaminases. Lack of associations between intra-abdominal fat or body mass index z-score and these metabolic parameters highlight the importance of fat distribution rather than fat quantity alone. The current study reveals the potential to index simultaneously ectopic fat in two organs important for glucose and lipid metabolism.

11:54 751

Fat Contents of Human Liver, Pancreas and Kidney
Paul E. Sijens1, Mireille A. Edens1, Stephan J.L. Bakker1, Ronald P. Stolk1
1UMCG, Groningen, Netherlands

Multivoxel MR spectroscopy and a previously validated gradient echo MRI adaptation of Dixon’s two-point technique were used to quantify kidney, liver, and pancreas fat contents in volunteers with diverse body weights, and to assess inter-organ relationships. Respective fat contents of liver, pancreas and kidney were 4.4%, 4.0% and 0.8%. The amount of subcutaneous fat correlated with liver fat content and pancreas fat content (r=0.45 and r=0.44, respectively; P<0.01). Kidney fat content correlated with none of the other parameters, indicating that renal lipid accumulation, unlike the coupled accumulations of fat in liver and pancreas (r=0.43;P<0.01), is not observed in obese subjects.

12:06 752.

Use of MRI for Longitudinal in Vivo Phenotyping of Obese Mouse Models Following a Dietary Intervention
Abdel Wahad Bidar1, Karolina Ploj2, Christopher Lelliott2, Karin Nelander3, Leonard Storlien2, Paul Hockings1
DECS Imaging, AstraZeneca R&D, Mölndal, Sweden; 2CVGI, Bioscience, AstraZeneca R&D, Sweden; 3DECS Discovery Statistics, AstraZeneca R&D, Sweden

In preclinical drug discovery, experimental rodent models of obesity are used for the investigation of metabolic disorders. Repeated in vivo measurements of adipose tissue depots and intraorgan fat can provide longitudinal data with greatly reduced usage of experimental animals. The aim of the present study was threefold: (i) validate in vivo MRI/S determinations of brown adipose tissue, total, intra-abdominal and subcutaneous white adipose tissues as well as intrahepatocellular lipids against ex vivo measurement, (ii) address the 3R’s mandate, by presenting a statistical power analysis; (iii) characterize the phenotypic and metabolic switch of the “cafeteria-diet” mouse model during a dietary intervention.

12:18 753

Real-Time Assessment of in Vivo Postprandial Lipid Storage in Rat Liver Using 1H-[13C] MRS
Richard Jonkers1, Tom Geraedts1, Luc van Loon2, Klaas Nicolay1, Jeanine Prompers1
Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; 2Department of Human Movement Sciences, Maastricht University Medical Centre+, Maastricht

Insulin resistance and type 2 diabetes are associated with elevated liver lipid content. It remains unknown whether this excessive accumulation of triglycerides is a result of increased lipid uptake or decreased lipid oxidation. In this study, we measured for the first time postprandial lipid storage in rat liver in vivo using localized 13C-edited 1H-observed MRS and 13C labeled lipids as tracers. The 13C enrichment of the liver lipid pool was 0.9 ± 0.7% at baseline and increased to 4.8 ± 0.9% 5h after ingestion of the tracer, showing that we can assess changes in 13C enriched lipid content in vivo.



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