Fat pipe fundamentals: managing bandwidth-hungry applications
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Highlights: • G.uralensis or licochalcone A reduced body weight and inguinal fat weights in obese mice. • G.uralensis or licochalcone A increased brown fat population in inguinal white adipose tissue of obese mice. • G.uralensis and LicoA reduce obesity and recover metabolic homeostasis by inducing fat browning. The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl{sub 2}) fraction was the most effective to induce expression of uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes. Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin, and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing obesity in mice by 6-week HFD, MeCl{sub 2} fraction of G. uralensis or LicoA was intraperitoneally administered for additional 19 days. MeCl{sub 2} fraction or LicoA significantly reduced body weight gain and inguinal fat pad weights. Furthermore, MeCl{sub 2} fraction or LicoA improved metabolic disorders induced by HFD as the treatments decreased serum levels of glucose and cholesterol, and blocked insulin resistance. MeCl{sub 2} fraction or LicoA enhanced expression of brown fat markers such as UCP1, PRDM16, and PGC-1α and increased brown fat phenotype population in inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA are effective to reduce obesity and to recover metabolic homeostasis by inducing the brown fat phenotype.
This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.
Purpose: To explore the feasibility of extracting the relative density from quantitative MRI measurements as well as estimate a correlation between the extracted measures and CT Hounsfield units. Methods: MRI has the ability to separate water and fat signals, producing two separate images for each component. By performing appropriate corrections on the separated images, quantitative measurement of water and fat mass density can be estimated. This work aims to test this hypothesis on 1.5T.Peanut oil was used as fat-representative, while agar as water-representative. Gadolinium Chloride III and Sodium Chloride were added to the agar solution to adjust the relaxation times and the medium conductivity, respectively. Peanut oil was added to the agar solution with different percentages: 0%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% and 100%. The phantom was scanned on 1.5T GE Optima 450W with the body coil using a multigradient echo sequences. Water/fat separation were performed while correcting for main field (B0) inhomogeneity and T{sub 2}* relaxation time. B1+ inhomogeneities were ignored. The phantom was subsequently scanned on a Philips Brilliance CT Big Bore. MR-corrected fat signal from all vials were normalized to 100% fat signal. CT Hounsfield values were then compared to those obtained from the normalized MR-corrected fat values as well as to the phantom for validation. Results: Good agreement were found between CT HU and the MR-extracted fat values (R{sup 2} = 0.98). CT HU also showed excellent agreement with the prepared fat fractions (R{sup 2}=0.99). Vials with 70%, 80%, and 90% fat percentages showed inhomogeneous distributions, however their results were included for completion. Conclusion: Quantitative MRI water/fat imaging can be potentially used to extract the relative tissue density. Further in-vivo validation are required.
The effects of 18.5 days of weightlessness on the body composition of young, growing, male laboratory rats were examined. Three groups of 5 rats each were examined. It is indicated that exposure of young, growing, male rats to 18.5 days of weightlessness produces: (1) no effect on the quantity of fat stored by the body; (2) a slight reduction in the quantity of fat free tissue laid down by the body; (3) a small reduction in the fraction of water contained by the fat free body mass; (4) a similar reduction in the fraction of water contained by the fat free skin and fat free carcass; (5) a shift in relative distribution of the total body water from skin to viscera; (6) a diminution in the fraction of extracellular water contained by the fat free body; (7) no effect on the fraction of total skeletal musculature contained by the fat free body, as indicated by body creatine content; (8) a sizeable reduction in the fraction of bone mineral contained by the fat free body, as calculated from body calcium content. The nature of the physiological changes induced by unloading from Earth gravity in the mammalian organism are illustrated.
Highlights: • The regulatory role of lncRNAs in fat deposition remains partially understood. • Investigation of lncRNAs expression level in intramuscular adipose tissues. • lncRNAs were implicated in pathways related to fat deposition and lipid metabolism. • A remarkable difference in fat metabolism in pigs. The regulatory role of long non-coding RNAs (lncRNAs) in various biological functions has been demonstrated. However, their role in fat deposition and lipid metabolism in pigs remains less understood. To explore the expression profile of lncRNAs in Jinhua and Landrace pigs, we investigated the expression levels of lncRNAs in intramuscular adipose tissues obtained from these pigs. Results showed that the expression levels of lncRNAs in these pig breeds significantly (Fold Change ≥ 2.0, FDR < 0.05) differed. A total of 4910 lncRNAs were identified, and 119 of these lncRNAs were differentially expressed. Of these differentially expressed lncRNAs, 60 and 59 were up- and down-regulated, respectively. The differentially expressed lncRNAs are involved in mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, PI3k-Akt signaling pathway. We then compared these differentially expressed lncRNAs with mRNAs and found that six of the co-expressed lncRNAs were implicated in pathways related to fat deposition and lipid metabolism. Overall, our results revealed a remarkable difference in fat metabolism in intramuscular adipose tissues of pigs, and provide a basis for subsequent research on fat deposition.
The study aim was to investigate the association between prenatal exposure to endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old Flemish children. The subjects were 114 Flemish children (50% boys) that took part in the first Flemish Environment and Health Study (2002–2006). Cadmium, PCBs, dioxins, p,p′-DDE and HCB were analysed in cord blood/plasma. When the child reached 7–9 years, height, weight, waist circumference and skinfolds were measured. Significant associations between prenatal exposure to EDCs and indicators of body composition were only found in girls. After adjustment for confounders and covariates, a significant negative association was found in girls between prenatal cadmium exposure and weight, BMI and waist circumference (indicator of abdominal fat) and the sum of four skinfolds (indicator of subcutaneous fat). In contrast, a significant positive association (after adjustment for confounders/covariates) was found between prenatal p,p′-DDE exposure and waist circumference as well as waist/height ratio in girls (indicators of abdominal fat). No significant associations were found for prenatal PCBs, dioxins and HCB exposure after adjustment for confounders/covariates. This study suggests a positive association between prenatal p,p′-DDE exposure and indicators of abdominal fat and a negative association between prenatal cadmium exposure and indicators of both abdominal as well as subcutaneous fat in girls between 7 and 9 years old. - Highlights: • Associations between prenatal contaminant exposure and anthropometrics in children. • Significant association only found in girls. • No significant associations found for prenatal PCBs, dioxins and HCB exposure. • Girls: negative association between cadmium and abdominal and subcutaneous fat. • Girls: positive association between p,p′-DDE and indicators of abdominal fat.
Purpose: Dixon sequences are used to characterize disease processes, obtain good fat or water separation in cases where fat suppression fails and to obtain pseudo-CT datasets. Dixon's method uses at least two images acquired with different echo times and thus requires prolonged acquisition times. To overcome associated problems (e.g., for DCE/cine-MRI), we propose to use a method for water/fat separation based on spectrally selective RF pulses. Methods: Two alternating RF pulses were used, that imposes a fat selective phase cycling over the phase encoding lines, which results in a spatial shift for fat in the reconstructed image, identical to that in CAIPIRINHA. Associated aliasing artefacts were resolved using the encoding power of a multi-element receiver array, analogous to SENSE. In vivo measurements were performed on a 1.5T clinical MR-scanner in a healthy volunteer's legs, using a four channel receiver coil. Gradient echo images were acquired with TE/TR = 2.3/4.7ms, flip angle 20°, FOV 45×22.5cm{sup 2}, matrix 480×216, slice thickness 5mm. Dixon images were acquired with TE,1/TE,2/TR=2.2/4.6/7ms. All image reconstructions were done in Matlab using the ReconFrame toolbox (Gyrotools, Zurich, CH). Results: RF pulse alternation yields a fat image offset from the water image. Hence the water and fat images fold over, which is resolved using in-plane SENSE reconstruction. Using the proposed technique, we achieved excellent water/fat separation comparable to Dixon images, while acquiring images at only one echo time. Conclusion: The proposed technique yields both inphase water and fat images at arbitrary echo times and requires only one measurement, thereby shortening the acquisition time by a factor 2. In future work the technique may be extended to a multi-band water/fat separation sequence that is able to achieve single point water/fat separation in multiple slices at once and hence yields higher speed-up factors.
Purpose: To determine the effects of left gastric artery embolization (LGAE) on computed tomography (CT) body composition change. Materials and methods: Sixteen overweight or obese patients who had abdominal CT scans before and after LGAE for gastric bleeding were retrospectively reviewed. Body composition analysis was performed with semiautomated imaging processing algorithms (MATLAB 13.0, Math Works, MA). Adipose tissue and lean skeletal muscle were measured using threshold attenuation values. Total body fat index (BFI), subcutaneous fat index (SFI), visceral fat index (VFI), intramuscular fat index (IMFI), and skeletal muscle index (SMI) were determined ([tissue area (cm)]{sup 2}/[height (m)]{sup 2}). Excess body weight (EBW) was determined based on the Lorentz formula for ideal body weight. Results: Mean follow-up was 1.5 ± 0.8 months. Following LGAE, patients experienced significantly decreased body weight (p = 0.003), BMI (p = 0.005), EBW (p = 0.003), BFI (p = 0.03), SFI (p = 0.03), and SMI (p < 0.001). Changes in VFI and IMFI did not significantly change (p = 0.13 and p = 0.83, respectively). Conclusions: Patients who underwent LGAE had significant unintended weight loss as a result of decreased body fat and skeletal muscle. Body composition analysis can readily assess the extent of fat loss and identify muscle wasting.
Background: Vinyl chloride (VC) causes toxicant-associated steatohepatitis at high exposure levels. Recent work by this group suggests that underlying liver disease may predispose the liver to VC hepatotoxicity at lower exposure levels. The most common form of underlying liver disease in the developed world is non-alcoholic fatty liver disease (NAFLD). It is well-known that the type of dietary fat can play an important role in the pathogenesis of NAFLD. However, whether the combination of dietary fat and VC/metabolites promotes liver injury has not been studied. Methods: Mice were administered chloroethanol (CE - a VC metabolite) or vehicle once, 10 weeks after being fed diets rich in saturated fatty acids (HSFA), rich in poly-unsaturated fatty acids (HPUFA), or the respective low-fat control diets (LSFA; LPUFA). Results: In control mice, chloroethanol caused no detectable liver injury, as determined by plasma transaminases and histologic indices of damage. In HSFA-fed mice, chloroethanol increased HSFA-induced liver damage, steatosis, infiltrating inflammatory cells, hepatic expression of proinflammatory cytokines, and markers of endoplasmic reticulum (ER) stress. Moreover, markers of inflammasome activation were increased, while markers of inflammasome inhibition were downregulated. In mice fed HPUFA all of these effects were significantly attenuated. Conclusions: Chloroethanol promotes inflammatory liver injury caused by dietary fatty acids. This effect is far more exacerbated with saturated fat, versus poly-unsaturated fat; and strongly correlates with a robust activation of the NLRP3 inflammasome in the saturated fed animals only. Taken together these data support the hypothesis that environmental toxicant exposure can exacerbate the severity of NAFLD/NASH. - Highlights: • CE promotes inflammatory liver injury caused by dietary fatty acids. • This effect is stronger with saturated than with unsaturated fatty acids. • Damage caused by saturated fat and CE correlates with inflammasome activation.
Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24 h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500 µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications. - Highlights: • Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER) and thus highly susceptible to ER stress. • We studied the effect of acute challenge with different fatty acids and doses typical to normal and obese states on ER stress. • Saturated palmitic acid significantly affected the ER UPR response demonstrated by; altered Xbp1 splicing, elevation in UPR transcripts levels and immune factors, Xbp1 protein level and Xbp1 time-depended nucleus translocation. • Poly and monounsaturated fatty acids demonstrated varying effects on ER stress markers. • Oleic acid demonstrate protective effect on pancreatic ER stress.