Assessment of Fat Accumulation and Mobilization during obesity and weight-loss Interventions in Rodents
Bhanu Prakash KN1, Venkatesh Gopalan1, Swee Shean Lee1, and Sendhil Velan S1,2

1Laboratory of Metabolic Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, 2Singapore Institute for Clinical Sciences, Singapore, Singapore

Synopsis

Quantification of adipose tissue distribution within the abdomen is fundamental for investigations in obesity and diabetes. Distribution of fat within the body, and its accumulation in the abdominal cavity, exert different physiologic effects based on their anatomical location. Calorie-restriction and exercise interventions improve obesity risk factors. Fat accumulation and mobilization can vary depending on the type and quality of fat in different locations. We have investigated the quantitative changes in fat volumes at different positions in the abdomen in diet induced obese rats.

Purpose

Understanding the distribution of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) within the abdomen is fundamental for the evaluation of obesity and diabetes. Expansion of SAT and VAT contributes to the metabolic syndrome including obesity and diabetes. VAT can be further compartmentalized as perirenal, mesentric, gonadal, retroperitoneal and intraperitoneal based on the locations in abdomen. During obesity these fat depots can contribute by secreting various bioactive molecules and hormones, such as adiponectin, leptin, tumour necrosis factor, resistin and interleutin 6 (IL-6)1.During weight loss interventions like exercise (EX) and calorie restriction (CR) these fat depots can vary in their response including secretion of hormones. Studies have shown that lipolysis is heterogeneous in different adipose tissue regions of SAT and VAT; with intra-abdominal VAT being most active 2, 3. During endurance exercise, the lipolysis rate is increased in upper abdominal SAT than in lower body SAT4. Loss of fat/weight is associated with improvements in risk factors of obesity5 making the identification of the measurement of SAT/VAT volume particularly important for calculating the change in SAT/VAT due to weight-loss interventions. Several studies utilize a single-slice image at L4–L5 to estimate the VAT. There have been arguments on which is the most suitable location for estimating the total volume of VAT using a single slice estimation6-8. In this study we have investigated the changes in accumulation and mobilization in different locations of the abdomen with exercise and diet interventions.

Methods

All in-vivo experiments were in compliance and approved by institutional animal care and use committee. In-vivo imaging was performed with a 7T Bruker Clinscan at two time points (pre- and post-scans) during the study. Transverse turbo spin echo (TSE) abdominal images (from L1 – L5 of the spine) of Fisher 344 rats, CLEA Japan were acquired during the study. The rats were fed with high fat diet from 5 to 18 weeks of age to induce obesity. The rodents were divided into 5 different cohorts (N = 7): control (CG), exercise (EX-1, EX 2; exercise once /twice a day), and calorie restriction (CR-15, CR-30; -15% and -30% reduction in calorie intake). The exercise intervention was induced by making the rodents to run for 30 minutes at a speed of 20m/min on a treadmill. The weight-loss interventions were performed for 4 weeks. The body weight was measured on weekdays and food intake was measured every day. Both scans (pre- and post-intervention) used the same protocol with an FOV of 65 X 65 mm, base resolution of 256 X 256. Segmentation of VAT and SAT was performed by an in-house developed hybrid algorithm which combined level set and fuzzy clustering methods9, 10. MATLAB was used to develop and implement the segmentation method. Statistical Analysis: The pre/post analysis of the MRI estimates of abdominal SAT and VAT volumes, and fat at each lumbar position for different interventions were analysed using ANCOVA. The post-intervention scores were used as the dependent variable with the pre-intervention scores as a covariate and the cohort as the fixed factor. Both pre/post analyses planned comparisons of the intervention groups were made with the high fat diet control group with a student’s t-test.

Results

The total SAT and VAT volume based analysis showed significance (p <0.05) for CR-30, EX-1 and EX-2 cohorts (Fig. 1 and 2), while the same was not reflected in the lumbar position based analysis. The percentage change in SAT and VAT volumes at different lumbar positions (L1-L5) for control group (CG), calorie restriction (CR-15, CR-30) and exercise (EX-1, EX_2) interventions are shown in Fig. 3. In the detailed lumbar based analysis, the percentage VAT change at all the lumbar positions (L1 – L5) in exercise groups (EX-1 and EX-2) was significant; whereas the CR-30 had significant changes in VAT at L5 and L3 positions only. SAT changes were significant for L1 and L3 sections in EX-1 and EX-2 cohorts; whereas calorie restriction cohorts did not have any significant changes in SAT.

Conclusions

We have quantitatively assessed the changes in SAT/VAT at each lumbar position due to weight-loss interventions of exercise and calorie restriction using MRI in high fat diet fed rat model. Our results demonstrate the nature of changes in the fat patterns for both calorie restriction and exercise interventions at each lumbar position. Our results show heterogeneity in fat accumulation and mobilization during obesity and weight-loss interventions. Hence, a detailed whole abdomen based analysis is required to accurately assess the response of various fat depots. The specific changes in SAT/VAT at each lumbar position might also influence the quality of fat.

Acknowledgements

No acknowledgement found.

References

[1] M. Mohsen Ibrahim. “Subcutaneous and visceral adipose tissue: structural and functional differences” Obesity reviews, 2010,11:11-18 [2] Coyle. “Fat Metabolism During Exercise”. Grad. Sports Inst. Vol 8(6). 1995. [3] Bertevello and Seelaender. “Heterogeneous response of adipose tissue to cancer cachexia”. Braz J Med Biol Res, Vol 34(9), Sept 2001, 1161-1167. [4] Horowitz, Jeffrey F. “Regulation of Lipid Mobilization and Oxidation during Exercise in Obesity”. Exercise & Sport Sciences Reviews. Vol 29(1), Jan 2001, 42-46. [5] Tresierras and Balady. “Resistance Training in the Treatment of Diabetes and Obesity: Mechanisms and Outcomes”. J Cardiopulmonary Rehabilitation & Prevention, Vol 29(2), March/April 2009, 67 – 75. [6] Poobalan, et al. “Long-term weight loss effects on all-cause mortality in verweight/obese populations”. Obes Rev Vol 8, 2007, 503–513. [7] Seidell JC, et al. “Assessment of intra-abdominal and subcutaneous abdominal fat: relation between anthropometry and computed tomography”. Am J Clin Nutr 1987, 45:7–13. [8] Irlbeck T, et al. “Association between single-slice measurements of visceral and abdominal subcutaneous adipose tissue with volumetric measurements: the ramingham heart study”. Int J Obes (Lond) 2010, 34:781–787. [9] Lee S,et al. “Interindividual variation in abdominal subcutaneous and visceral adipose tissue: influence of measurement site”. J Appl Physiol 2004, 97:948–954. [10] Bhanu Prakash KN et al. “Quantification of Abdominal Fat Depots in Rats and Mice during Obesity and Weight Loss Interventions”. PLOS One, October 13, 2014.

Figures

Distribution of SAT and VAT at different lumbar positions (L1 - L5)

Results based on total volume of SAT & VAT between L1 – L5.

Results based on individual lumbar position SAT & VAT for different cohorts (CG, CR-15, CR-30, EX-1, and EX-2).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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