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At least 19 records

Validation of a DIXON-based fat quantification technique for the measurement of visceral fat using a CT-based reference standard

Purpose: The purpose of the study is to determine whether a novel semi-automated DIXON-based fat quantification algorithm can reliably quantify visceral fat using a CT-based reference standard. Methods: This was an IRB-approved retrospective cohort study of 27 subjects who underwent abdominopelvic CT within 7 days of proton density fat fraction (PDFF) mapping on a 1.5T MRI. Cross-sectional visceral fat area per slice (cm{sup 2}) was measured in blinded fashion in each modality at intervertebral disc levels from T12 to L4. CT estimates were obtained using a previously published semi-automated computational image processing system that sums pixels with attenuation − 205 to − 51 HU. MR estimates were obtained using two novel semi-automated DIXON-based fat quantification algorithms that measure visceral fat area by spatially regularizing non-uniform fat-only signal intensity or de-speckling PDFF 2D images and summing pixels with PDFF ≥ 50%. Pearson’s correlations and Bland–Altman analyses were performed. Results: Visceral fat area per slice ranged from 9.2 to 429.8 cm{sup 2} for MR and from 1.6 to 405.5 cm{sup 2} for CT. There was a strong correlation between CT and MR methods in measured visceral fat area across all studied vertebral body levels (r = 0.97; n = 101 observations); the least (r = 0.93) correlation was at T12. Bland–Altman analysis revealed a bias of 31.7 cm{sup 2} (95% CI [− 27.1]–90.4 cm{sup 2}), indicating modestly higher visceral fat assessed by MR. Conclusion: MR- and CT-based visceral fat quantification are highly correlated and have good cross-modality reliability, indicating that visceral fat quantification by either method can yield a stable and reliable biomarker.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Oral lipase activities and fat-taste receptors for fat-taste sensing in chickens

Highlights: • We cloned a fat-taste receptor candidate gene, CD36, from chickens. • Fat-taste receptor genes, GPR120 and CD36, were expressed in chicken oral tissues. • Several lipase genes were expressed in chicken oral tissues. • Chicken oral tissues contained functional lipases. It has been reported that a functional fat-taste receptor, GPR120, is present in chicken oral tissues, and that chickens can detect fat taste in a behavioral test. However, although triglycerides need to be digested to free fatty acids to be recognized by fat-taste receptors such as GPR120, it remains unknown whether lipase activities exist in chicken oral tissues. To examine this question, we first cloned another fat-taste receptor candidate gene, CD36, from the chicken palate. Then, using RT-PCR, we determined that GPR120 and CD36 were broadly expressed in chicken oral and gastrointestinal tissues. Also by RT-PCR, we confirmed that several lipase genes were expressed in both oral and gastrointestinal tissues. Finally, we analyzed the lipase activities of oral tissues by using a fluorogenic triglyceride analog as a lipase substrate. We found there are functional lipases in oral tissues as well as in the stomach and pancreas. These results suggested that chickens have a basic fat-taste reception system that incorporates a triglycerides/oral-lipases/free fatty acids/GPR120 axis and CD36 axis.

60 APPLIED LIFE SCIENCES↗

Characterization of fat metabolism in the fatty liver caused by a high-fat, low-carbohydrate diet: A study under equal energy conditions

The pathology of fatty liver due to increased percentage of calories derived from fat without increased overall caloric intake is largely unclear. In this study, we aimed to characterize fat metabolism in rats with fatty liver resulting from consumption of a high-fat, low-carbohydrate (HFLC) diet without increased caloric intake. Four-week-old male Sprague-Dawley rats were randomly assigned to the control (Con) and HFLC groups, and rats were fed the corresponding diets ad libitum. Significant decreases in food intake per gram body weight were observed in the HFLC group compared with that in the Con group. Thus, there were no significant differences in body weights or caloric intake per gram body weight between the two groups. Marked progressive fat accumulation was observed in the livers of rats in the HFLC group, accompanied by suppression of de novo lipogenesis (DNL)-related proteins in the liver and increased leptin concentrations in the blood. In addition, electron microscopic observations revealed that many lipid droplets had accumulated within the hepatocytes, and mitochondrial numbers were reduced in the hepatocytes of rats in the HFLC group. Our findings confirmed that consumption of the HFLC diet induced fatty liver, even without increased caloric intake. Furthermore, DNL was not likely to be a crucial factor inducing fatty liver with standard energy intake. Instead, ultrastructural abnormalities found in mitochondria, which may cause a decline in β-oxidation, could contribute to the development of fatty liver. - Highlights: • The high-fat, low-carbohydrate diet did not affect body weight or caloric intake. • The high-fat, low-carbohydrate diet caused fatty liver in rats. • De novo lipogenesis was not a crucial factor in fatty liver. • Mitochondria were altered in fatty livers of rats consuming this diet.

60 APPLIED LIFE SCIENCES↗

Measurement of spleen fat on MRI-proton density fat fraction arises from reconstruction of noise

Purpose: This study compares splenic proton density fat fraction (PDFF) measured using confounder-corrected chemical shift-encoded (CSE)-MRI to magnetic resonance spectroscopy (MRS) in human patients at 3T. Methods: This was a prospectively designed ancillary study to various previously described single-center studies performed in adults and children with known or suspected nonalcoholic fatty liver disease. Patients underwent magnitude-based MRI (MRI-M), complex-based MRI (MRI-C), high signal-to-noise variants (Hi-SNR MRI-M and Hi-SNR MRI-C), and MRS at 3T for spleen PDFF estimation. PDFF from CSE-MRI methods were compared to MRS-PDFF using Wilcoxon signed-rank tests. Demographics were summarized descriptively. Spearman’s rank correlations were computed pairwise between CSE-MRI methods. Individual patient measurements were plotted for qualitative assessment. A significance level of 0.05 was used. Results: Forty-seven patients (20 female, 27 male) including 12 adults (median 55 years old) and 35 children (median 12 years old). Median PDFF estimated by MRS, MRI-M, Hi-SNR MRI-M, MRI-C, and Hi-SNR MRI-C was 1.0, 2.3, 1.9, 2.2, and 2.0%. The four CSE-MRI methods estimated statistically significant higher spleen PDFF values compared to MRS (p < 0.0001 for all). Pairwise associations in spleen PDFF values measured by different CSE-MRI methods were weak, with the highest Spearman’s rank correlations being 0.295 between MRI-M and Hi-SNR MRI-M; none were significant after correction for multiple comparisons. No qualitative relationship was observed between PDFF measurements among the various methods. Conclusion: Overestimation of PDFF by CSE-MRI compared to MRS and poor agreement between related CSE-MRI methods suggest that non-zero PDFF values in human spleen are artifactual.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Chicken fat for catalysis: a scaffold is as important for molecular complexes for energy transformations as it is for enzymes in catalytic function

Metalloenzymes are remarkably active, specific, and efficient catalysts.Mimicking the active sites with organometallic complexes based on crystal structures has been a focus for many synthetic chemists. These surrogates have provided significant mechanistic insight into both the molecular complexes as well as the enzymes, however, one of the principle findings has been that just reproducing the active site is not adequate in reproducing the catalytic function. Specifically, the scaffold surrounding the active site plays a critical role in many aspects of catalysis, from positioning reactants optimally to positioning functional groups for reaction to creating the ideal environment for catalysis. Each of these can be controlled with both static positioning as well as small and large dynamics that can activate or control a specific part of the reaction. In this review, we will discuss the effect of organic/peptidic scaffolds, along with medium as an extension of the scaffold, and their varying impacts on catalytic reactivity.

Laureanti, Joseph A.↗

Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat. • The inflammatory signal pathway were more activated in aged animal visceral than subcutaneous fat. • The results suggested visceral fat is involved in inflammation-induced diseases in the elderly.

60 APPLIED LIFE SCIENCES↗

Macrophage infiltration regulates the adipose ECM reconstruction and the fibrosis process after fat grafting

Background: Fat grafting experiences a regeneration process from free lipoaspirate to intact adipose tissue. The adipose extracellular matrixes (ECM) provide the structure and biochemical support for surrounding cells; inflammatory cells, like macrophages, regulate the process. Our hypothesis states that transferred fat undergoes ECM remodeling after fat grafting and this process is regulated by macrophage infiltration. Methods: Lipoaspirate was injected subcutaneously into the back of nude mice. The micro-structure of the fat grafts was observed and evaluated using scanning electron microscope (SEM) and collagen I immunohistostaining. The gene transcription level of collagen proteins and the matrix metalloproteinases (MMPs) were assessed by qRT-PCR. Local injection of clodronate-encapsulated liposome was used to evaluate the role of macrophages of fat grafts at different stages in ECM remodeling, depletion of macrophages, at different time points (Week 1 and Week 4). Results: Results from the SEM analysis showed that liposuction caused severe damage to the ECM structure in freshly aspirated adipose tissue. On Day 1 post-transplantation, the surface of adipocytes was covered with platelets and this secreted fibrin network on the fat grafts. An integral adipose structure was already established with an intact ECM at the end of Week 1. The early depletion of macrophages remarkably hindered ECM reconstruction process by down-regulating the expression of collagen proteins and MMPs. Expression of Collagen I was significantly decreased after depletion of macrophages in both gene and protein levels. Results also showed that the depletion of macrophages at the later stage of fat grafting resulted in less fibrosis and capsule formation. Conclusion: Free fat aspirates undergo a prompt ECM reconstruction process and completed in the first week; this process can be initiated with platelets and mainly modulated by inflammatory cells such as macrophages. It was also observed that prolonged macrophage infiltration contributes to fibrosis and capsule formation in fat grafts. - Highlights: • Free fat aspirates undergo a prompt ECM reconstruction process in the first week. • The ECM reconstruction process is initiated with platelets and modulated by macrophages. • Depletion of macrophage in transferred fat resulted in delayed ECM reconstruction.

60 APPLIED LIFE SCIENCES↗

Short- and long-term effects of high-fat diet feeding and voluntary exercise on hepatic lipid metabolism in mice

Highlights: • Voluntary exercise for 1 week (short-term exercise) significantly reduced fat accumulation in the liver. • Short-term exercise induced a downregulation of lipogenic proteins and an upregulation of lipolytic proteins in liver. • Long-term voluntary exercise downregulated the expression of hepatic lipogenesis-associated proteins. Exercise is an effective tool for improving high-fat diet induced fat accumulation in the liver. However, the process of fat accumulation in the liver and the efficacy of early intervention with exercise remain unclear. The aim of this study was to investigate the short- and long-term effects of high-fat diet feeding and voluntary exercise on hepatic lipid metabolism in mice. Male C57BL/6J mice aged 6 weeks were randomly divided into two groups, the control group and high-fat diet feeding group, and fed a normal or high-fat diet for 12 weeks. After 6 weeks, mice in the high-fat diet feeding group were further divided into no exercise group and voluntary exercise training group, with mice in the exercise group provided a running wheel for 6 weeks. Body weight, food intake, and wheel rotation counts were measured every second day for 12 weeks. We found that voluntary exercise for 1 week (short-term exercise) significantly reduced fat accumulation in the liver by downregulating the expression of hepatic lipogenesis-associated proteins and upregulating the expression of hepatic lipolysis-associated proteins, as determined through western blotting and histology. Further, voluntary exercise for 6 weeks (long-term exercise) downregulated the expression of hepatic lipogenesis-associated proteins. These results suggest that hepatic lipogenesis and/or hepatic lipolysis mediate the beneficial effects of voluntary exercise on hepatic fat accumulation.

60 APPLIED LIFE SCIENCES↗

The splicing factor transformer2 (tra2) functions in the Drosophila fat body to regulate lipid storage

Highlights: • Transformer2 (tra2) is a splicing protein whose metabolic functions are unknown. • Tra2 functions in the Drosophila fat body to modulate triglyceride levels. • Decreasing tra2 in the fat body promotes starvation resistance. • Tra2 alters CPT1 splicing in the fly fat body. Excess nutrients are stored as triglycerides mainly in the adipose tissue of an animal and these triglycerides are located in structures called lipid droplets. Previous genome-wide RNAi screens in Drosophila cells identified splicing factors as playing a role in lipid droplet formation. Our lab has recently identified the SR protein, 9G8, as an important factor in fat storage as decreasing its levels results in augmented triglyceride storage in the fat body. Previous in vitro studies have implicated 9G8 in the regulation of splicing of the sex determination gene doublesex (dsx) by binding to transformer (tra) and transformer2 (tra2); however, any function of these sex determination proteins in regulating metabolism is unknown. In this study, we have uncovered a role of tra2 to regulate fat storage in vivo. Inducing tra2{sup dsRNA} in the adult fat body resulted in an increase in triglyceride levels but had no effect on glycogen storage. Consistent with the triglyceride phenotype, tra2 knockdown flies lived longer under starvation conditions. In addition, this increase in triglycerides is due to more fat storage per cell and not an increase in the number of fat cells. Interestingly, the splicing of CPT1, an enzyme involved in the breakdown of lipids, was altered in flies with decreased tra2. The less-catalytically active isoform of CPT1 accumulated in tra2{sup dsRNA} flies suggesting a decrease in lipid breakdown, which is consistent with the increased triglyceride levels observed in these flies. Together, these results suggest a link between mRNA splicing, sex determination and lipid metabolism and may provide insight into the mechanisms underlying tissue-specific splicing and nutrient storage.

60 APPLIED LIFE SCIENCES↗

Influence of amplitude-related perfusion parameters in the parotid glands by non-fat-saturated dynamic contrast-enhanced magnetic resonance imaging

Purpose: To verify whether quantification of parotid perfusion is affected by fat signals on non-fat-saturated (NFS) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and whether the influence of fat is reduced with fat saturation (FS). Methods: This study consisted of three parts. First, a retrospective study analyzed DCE-MRI data previously acquired on different patients using NFS (n = 18) or FS (n = 18) scans. Second, a phantom study simulated the signal enhancements in the presence of gadolinium contrast agent at six concentrations and three fat contents. Finally, a prospective study recruited nine healthy volunteers to investigate the influence of fat suppression on perfusion quantification on the same subjects. Parotid perfusion parameters were derived from NFS and FS DCE-MRI data using both pharmacokinetic model analysis and semiquantitative parametric analysis. T tests and linear regression analysis were used for statistical analysis with correction for multiple comparisons. Results: NFS scans showed lower amplitude-related parameters, including parameter A, peak enhancement (PE), and slope than FS scans in the patients (all with P < 0.0167). The relative signal enhancement in the phantoms was proportional to the dose of contrast agent and was lower in NFS scans than in FS scans. The volunteer study showed lower parameter A (6.75 ± 2.38 a.u.), PE (42.12% ± 14.87%), and slope (1.43% ± 0.54% s{sup −1}) in NFS scans as compared to 17.63 ± 8.56 a.u., 104.22% ± 25.15%, and 9.68% ± 1.67% s{sup −1}, respectively, in FS scans (all with P < 0.005). These amplitude-related parameters were negatively associated with the fat content in NFS scans only (all with P < 0.05). Conclusions: On NFS DCE-MRI, quantification of parotid perfusion is adversely affected by the presence of fat signals for all amplitude-related parameters. The influence could be reduced on FS scans.

60 APPLIED LIFE SCIENCES↗

SU-F-J-112: Clinical Feasibility Test of An RF Pulse-Based MRI Method for the Quantitative Fat-Water Segmentation

Purpose: Quantitative fat-water segmentation is important not only because of the clinical utility of fat-suppressed MRI images in better detecting lesions of clinical significance (in the midst of bright fat signal) but also because of the possible physical need, in which CT-like images based on the materials’ photon attenuation properties may have to be generated from MR images; particularly, as in the case of MR-only radiation oncology environment to obtain radiation dose calculation or as in the case of hybrid PET/MR modality to obtain attenuation correction map for the quantitative PET reconstruction. The majority of such fat-water quantitative segmentations have been performed by utilizing the Dixon’s method and its variations, which have to enforce the proper settings (often predefined) of echo time (TE) in the pulse sequences. Therefore, such methods have been unable to be directly combined with those ultrashort TE (UTE) sequences that, taking the advantage of very low TE values (∼ 10’s microsecond), might be beneficial to directly detect bones. Recently, an RF pulse-based method (http://dx.doi.org/10.1016/j.mri.2015.11.006), termed as PROD pulse method, was introduced as a method of quantitative fat-water segmentation that does not have to depend on predefined TE settings. Here, the clinical feasibility of this method is verified in brain tumor patients by combining the PROD pulse with several sequences. Methods: In a clinical 3T MRI, the PROD pulse was combined with turbo spin echo (e.g. TR=1500, TE=16 or 60, ETL=15) or turbo field echo (e.g. TR=5.6, TE=2.8, ETL=12) sequences without specifying TE values. Results: The fat-water segmentation was possible without having to set specific TE values. Conclusion: The PROD pulse method is clinically feasible. Although not yet combined with UTE sequences in our laboratory, the method is potentially compatible with UTE sequences, and thus, might be useful to directly segment fat, water, bone and air.

60 APPLIED LIFE SCIENCES↗

Amelioration of UVB-induced oxidative stress and inflammation in fat-1 transgenic mouse skin

ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in fish oils, are known to scavenge lipid peroxyl radicals and potentiate host immune defence. As UVB-induced oxidative stress and inflammation have been implicated in apoptotic cell death, this study was aimed to investigate the anti-inflammatory, anti-oxidative, and anti-apoptotic capacity of fat-1 transgenic mice capable of converting ω-6 to ω-3 PUFAs. Wild-type (WT) C57BL/6 mice and fat-1 mice were maintained on the AIN-93 diet supplemented with 10% safflower oil rich in ω-6 PUFAs for 5 weeks. The ω-3/ω-6 PUFA ratio was significantly higher in the dorsal skin of fat-1 mice than that in the WT mice. Upon single exposure to UVB (5.0 kJ/m{sup 2}) radiation, fat-1 mice showed inflammatory as well as oxidative tissue damage and the expression of pro-inflammatory enzymes, cyclooxygenases-2 and inducible nitric oxide synthase in the skin to a much lesser extent than the WT mice. The protection of fat-1 mice from UVB-induced skin inflammation was associated with decreased phosphorylation of STAT3. Moreover, UVB-induced apoptosis was attenuated in fat-1 mouse skin. In comparison to WT animals, higher levels of Nrf2 and its target proteins, such as heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and thioredoxin-1, were found in the skin of fat-1 mice.

60 APPLIED LIFE SCIENCES↗

Effectiveness of fat grafting in scar reduction: A systematic review and meta‐analysis

Abstract Background Scar brings great physical and mental pain to patients. Fat grafting may be a new and simple way to treat scar. This review aimed to systematically evaluate the correlation between fat grafting and scar reduction. Methods The author searched Chinese and English literature databases such as CNKI, Wanfang Data, Cqvip, Pubmed, Web of Science, Embase, CBM, etc. for articles published in the period from 2011 to 2021 about the randomized controlled trials (RCTs) to assess the effect of fat grating on scar reduction, and then performed meta‐analysis with Review Manager 5.4. Results A total of nine articles were included in the assessment of the effect of fat grafting on scar reduction, with meta‐analysis suggesting statistical significance (OR = 5.63, 95% CI: 3.01–10.53, p < 0.01). There was statistical significance in the difference observed between the simple fat grating group ( p = 0.004) and the group of existing therapies combined with fat grafting ( p < 0.0001). Conclusion Fat grafting may be a good method for scar treatment, especially when it's combined with other therapies. Still, due to the limitations of included RCTs, more large‐scale high‐quality RCTs must be carried out before solid conclusions can be drawn.

Zhang, Xiaoyuan↗