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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

WE-AB-204-04: Feature Selection and Clustering Optimization for Pseudo-CT Generation in MR-Based Attenuation Correction and Radiation Therapy Planning

Purpose: Accurate and robust photon attenuation derived from MR is essential for PET/MR and MR-based radiation treatment planning applications. Although the fuzzy C-means (FCM) algorithm has been applied for pseudo-CT generation, the input feature combination and the number of clusters have not been optimized. This study aims to optimize both for clinically practical pseudo-CT generation. Methods: Nine volunteers were recruited. A 190-second, single-acquisition UTE-mDixon with 25% (angular) sampling and 3D radial readout was performed to acquire three primitive MR features at TEs of 0.1, 1.5, and 2.8 ms: the free-induction-decay (FID), the first and the second echo images. Three derived images, Dixon-fat and Dixon-water generated by two-point Dixon water/fat separation, and R2* (1/T2*) map, were also created. To identify informative inputs for generating a pseudo-CT image volume, all 63 combinations, choosing one to six of the feature images, were used as inputs to FCM for pseudo-CT generation. Further, the number of clusters was varied from four to seven to find the optimal approach. Mean prediction deviation (MPD), mean absolute prediction deviation (MAPD), and correlation coefficient (R) of different combinations were compared for feature selection. Results: Among the 63 feature combinations, the four that resulted in the best MAPD and R were further compared along with the set containing all six features. The results suggested that R2* and Dixon-water are the most informative features. Further, including FID also improved the performance of pseudo-CT generation. Consequently, the set containing FID, Dixon-water, and R2* resulted in the most accurate, robust pseudo-CT when the number of cluster equals to five (5C). The clusters were interpreted as air, fat, bone, brain, and fluid. The six-cluster Result additionally included bone marrow. Conclusion: The results suggested that FID, Dixon-water, R2* are the most important features. The findings can be used to facilitate pseudo-CT generation for unsupervised clustering. Please note that the project was completed with partial funding from the Ohio Department of Development grant TECH 11-063 and a sponsored research agreement with Philips Healthcare that is managed by Case Western Reserve University. As noted in the affiliations, some of the authors are Philips employees.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Generation of brain pseudo-CTs using an undersampled, single-acquisition UTE-mDixon pulse sequence and unsupervised clustering

Purpose: MR-based pseudo-CT has an important role in MR-based radiation therapy planning and PET attenuation correction. The purpose of this study is to establish a clinically feasible approach, including image acquisition, correction, and CT formation, for pseudo-CT generation of the brain using a single-acquisition, undersampled ultrashort echo time (UTE)-mDixon pulse sequence. Methods: Nine patients were recruited for this study. For each patient, a 190-s, undersampled, single acquisition UTE-mDixon sequence of the brain was acquired (TE = 0.1, 1.5, and 2.8 ms). A novel method of retrospective trajectory correction of the free induction decay (FID) signal was performed based on point-spread functions of three external MR markers. Two-point Dixon images were reconstructed using the first and second echo data (TE = 1.5 and 2.8 ms). R2{sup ∗} images (1/T2{sup ∗}) were then estimated and were used to provide bone information. Three image features, i.e., Dixon-fat, Dixon-water, and R2{sup ∗}, were used for unsupervised clustering. Five tissue clusters, i.e., air, brain, fat, fluid, and bone, were estimated using the fuzzy c-means (FCM) algorithm. A two-step, automatic tissue-assignment approach was proposed and designed according to the prior information of the given feature space. Pseudo-CTs were generated by a voxelwise linear combination of the membership functions of the FCM. A low-dose CT was acquired for each patient and was used as the gold standard for comparison. Results: The contrast and sharpness of the FID images were improved after trajectory correction was applied. The mean of the estimated trajectory delay was 0.774 μs (max: 1.350 μs; min: 0.180 μs). The FCM-estimated centroids of different tissue types showed a distinguishable pattern for different tissues, and significant differences were found between the centroid locations of different tissue types. Pseudo-CT can provide additional skull detail and has low bias and absolute error of estimated CT numbers of voxels (−22 ± 29 HU and 130 ± 16 HU) when compared to low-dose CT. Conclusions: The MR features generated by the proposed acquisition, correction, and processing methods may provide representative clustering information and could thus be used for clinical pseudo-CT generation.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

Utilization of [14C]phenylalanine derived from arylphorin or free amino acid in Manduca sexta pharate adults

The role of arylphorin as a storage protein was studied using 14C-arylphorin. 14C-arylphorin was produced optimally by incubating one-half fat body from Manduca sexta fifth instar larvae at 22 degrees C for 24 h, in 1 ml of medium containing amino acids at 25% of their physiological concentration with [U-14C]-phenylalanine (phe) provided initially without nonlabeled phenylalanine. Nonlabeled phe was provided after 1 h at 16% of its physiological concentration. The specific activity of 14C-arylphorin produced in vitro was 30 times greater than that generated in vivo. Injection of 14C-arylphorin into pharate adults was used to study the distribution of 14C-phe derived from this protein into 14CO2 and tissues for comparison with injection of free 14C-phe during the middle (days 6 to 12 pharate adult) and late (days 12 to 17 pharate adult) stages of adult development. Appearance of 14CO2 from 14C-arylphorin as compared to 14C-phenylalanine showed a slower time course during both the middle and late stages of development, in keeping with the time needed for degradation of the protein. In accord with faster phe turnover near the end of adult development, total 14CO2 production was greater and the retention of 14C in hemolymph and fat body was less compared to the middle stage of development regardless of whether 14C-arylphorin or 14C-phe was injected. In the middle stage of development, the appearance of 14C in the cuticle and head parts was greater, whereas incorporation into abdomen and thorax was less than during the late stage of development. Since the pattern of 14C distribution from 14C-arylphorin and 14C-phe was similar, one major function of arylphorin must be as a storage protein replenishing the supply of free amino acids used for synthesis of adult tissues. These results also suggest a limited contribution of M. sexta arylphorin to formation of the cuticle subsequent to day-6 pharate adult.

Non-NASA Center↗
NASA NTRS1993

Temporal expression and immunogold localization of Plodia interpunctella granulosis virus structural proteins

Monospecific antisera were produced against four structural proteins (VP12, VP17, VP31, and granulin) of the Plodia interpunctella granulosis virus using polypeptides derived by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or acid extraction. The antisera were shown to be specific on immunoblots of SDS-PAGE separated granulosis virus and were further used to detect structural proteins in infected fat body lysates. Immunoblots of fat body lysates from early stages of infection indicated that VP12, VP17, VP31, and granulin were expressed by 2.5 days post-infection. Immunogold labeling of the virus using the monospecific antisera and electron microscopy confirmed earlier reports that granulin is located in the protein matrix, V17 is an envelope protein, and VP31 is a capsid protein.

Non-NASA Center↗
DOE OSTI2019

Thick branes in extra dimensions and suppressed dark couplings

The nature of dark matter (DM) and how it may interact with the various fields of the Standard Model (SM) remains a mystery. In this paper we show that the interaction between new light dark matter mediators and the SM particles can be naturally suppressed if one employs a single, flat extra dimension (ED). In this setup, the SM fields are localized in a finite width ‘fat’ brane, similar to models of Universal Extra Dimensions (UED), while DM, in turn, is confined to a thin brane at the opposite end of the ED interval. Including brane localized kinetic terms on the fat brane for the mediator fields, the resulting coupling between the SM and these light mediators can be several orders of magnitude smaller than the corresponding ones between the mediators and DM which we assume to be a typical gauge coupling. We investigate the implications of this scenario for both vector (i.e, dark photon, DP) and scalar mediator fields in the 5-D bulk. In this setup kinetic mixing, which is usually employed to suppress light mediator couplings, is not required. Here we assume that the SM particles couple to the DP via their B - L charges while the DP couples to the DM via a dark charge. Both the vector DP couplings and the corresponding Higgs portal couplings with the SM are shown to be natural small in magnitude with a size dependent on ratio of the 5-D compactification radius, R -1 ~ 0.1-1 GeV, and the SM brane thickness, L -1 ~ 2-10 TeV, a range chosen to avoid LHC and other experimental constraints. In this framework one can obtain the observed value of the DM relic abundance for a wide range of parameter choices, while the constrains due to direct DM detection and the invisible width of the Higgs do not impose significant challenges to the model. Finally, this mechanism can lead to distinct signatures in both present and upcoming experiments as it combines some common features of UED and DP models in a single ED setup.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2018

Detecting a boosted diboson resonance

New light scalar particles in the mass range of hundreds of GeV, decaying into a pair of W/Z bosons can appear in several extensions of the SM. The focus of collider studies for such a scalar is often on its direct production, where the scalar is typically only mildly boosted. The observed W/Z are therefore well-separated, allowing analyses for the scalar resonance in a standard fashion as a low-mass diboson resonance. In this work we instead focus on the scenario where the direct production of the scalar is suppressed, and it is rather produced via the decay of a significantly heavier (a few TeV mass) new particle, in conjunction with SM particles. Such a process results in the scalar being highly boosted, rendering the W/Z’s from its decay merged. The final state in such a decay is a “fat” jet, which can be either four pronged (for fully hadronic W/Z decays), or may be like a W/Z jet, but with leptons buried inside (if one of the W/Z decays leptonically). In addition, this fat jet has a jet mass that can be quite different from that of the W/Z/Higgs/top quark-induced jet, and may be missed by existing searches. In this work, we develop dedicated algorithms for tagging such multi-layered “boosted dibosons” at the LHC. As a concrete application, we discuss an extension of the standard warped extra dimensional framework where such a light scalar can arise. We demonstrate that the use of these algorithms gives sensitivity in mass ranges that are otherwise poorly constrained.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2019

Evaluating the structural complexity of isomeric bile acids with ion mobility spectrometry

Bile acids (BAs) play an integral role in digestion through the absorption of nutrients, emulsification of fats and fat-soluble vitamins, and maintenance of cholesterol levels. Metabolic disruption, diabetes, colorectal cancer, and numerous other diseases have been linked with BA disruption, making improved BA analyses essential. To date, most BA measurements are performed using liquid chromatography separations in conjunction with mass spectrometry measurements (LC-MS). However, 10–40 min LC gradients are often used for BA analyses and these may not even be sufficient for distinguishing all the important isomers present in the human body. Ion mobility spectrometry (IMS) is a promising tool for BA evaluations due to its ability to quickly separate isomeric molecules with subtle structural differences. In this study, we utilized drift tube IMS (DTIMS) coupled with MS to characterize 56 different unlabeled BA standards and 16 deuterated versions. In the DTIMS-MS analyses of 12 isomer groups, BAs with smaller m/z values were easily separated in either their deprotonated or sodiated forms (or both). However, as the BAs grew in m/z value, they became more difficult to separate with two isomer groups being inseparable. Metal ions such as copper and zinc were then added to the overlapping BAs, and due to different binding sites, the resulting complexes were separable. Thus, the rapid structural measurements possible with DTIMS-MS show great potential for BAs measurements with and without prior LC separations.

Zheng, Xueyun↗
DOE OSTI2019

Duodenal obstruction induced by retroperitoneal progression of bladder cancer: a report of two cases

Bladder cancer usually forms a papillary structure. Progression along the cavity or membranous structures surrounding the bladder, rectum, or retroperitoneum without formation of a discrete mass is rare. We here present two patients with duodenal obstruction caused by retroperitoneal progression of bladder cancer, in both of whom computed tomography revealed bladder and rectal wall thickening with a malignant target sign, thickened mesorectal fascia with abnormal tissue stranding, and increased perirectal fat density. Both cancers progressed despite treatment, as indicated by faint abnormal tissue stranding and increased retroperitoneal fat density along the retromesenteric plane from the pelvis to the duodenum. Subsequently, both patients developed obstruction in the horizontal portion of the duodenum, still without formation of a mass lesion. These two patients highlight the challenges associated with retroperitoneal invasion by bladder cancer in the absence of a mass lesion and underscore the importance of considering cancer progression in patients with bowel obstruction, even when there is no obvious mass lesion and/or only minor retroperitoneal findings. Progression along the retromesenteric plane may be the key pathway via which progressive bladder cancer results in duodenal obstruction without or with a minor mass lesion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Ischiorectal fossa: benign and malignant neoplasms of this “ignored” radiological anatomical space

Purpose: To review the pertinent anatomy and the imaging features of common and uncommon benign and malignant neoplasms and masses of the ischiorectal fossa. Results: The ischiorectal or ischioanal fossa is the largest space in the anorectal region. The benign neoplasms that develop in the ischiorectal originate from the different components that forms the fossa including vascular tumors such as aggressive angiomyxoma or hemangioma; neural tumors as plexiform neurofibroma or schwannoma; fat tumors as lipoma; skin/skin appendages tumors as hidradenoma papilliferum; smooth or skeletal muscle tumors as solitary fibrous tumor. The malignant neoplasms that develop in the ischiorectal fossa also originate from different components that forms the fossa including vascular tumors such as angiosarcoma, neural tumors as malignant granular cell tumor and malignant peripheral nerve sheath tumor; fat tumors as liposarcoma; smooth or skeletal muscle tumors as leiomyosarcoma, rhabdomyosarcoma, malignant PEComa, or undifferentiated pleomorphic sarcoma. Additionally, the ischiorectal fossa can also harbor secondary hematogenous metastases and be affected by direct invasion from neoplasms of adjacent pelvic organs and structures. Furthermore, other miscellaneous masses can occur in the ischiorectal fossa including congenital and developmental lesions, and inflammatory and infectious processes. Conclusion: Knowledge of the anatomy, and the spectrum of imaging findings of common and uncommon benign and malignant neoplasms of the ischiorectal fossa is crucial for the radiologists during interpretation of images allowing them to make contributions to the diagnosis and better patient management.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Metal Artifact Reduction for Orthopedic Prosthesis in Lower Extremity CT Venography: Evaluation of Image Quality and Vessel Conspicuity

Purpose: This study evaluates the image quality of lower extremity CT venography reconstructed with orthopedic metal artifact reduction (O-MAR) in patients with unilateral or bilateral metallic prostheses in the hip or knee. Methods: This retrospective study was approved by our institutional review board, and informed consent was waived. Twenty-nine patients of lower extremity CT with 51 metallic hip or knee prostheses were reconstructed to both standard CT images and O-MAR images. The subjective image quality and vessel conspicuity for both images were evaluated by two readers using five-point scales (0–4). Vessel conspicuity scores of 3 or 4 were considered diagnostically acceptable. Image noise was measured in the air and subcutaneous fat. Results: O-MAR images showed significantly higher scores of subjective image quality (p < .001) and vessel conspicuity (p = .002) than standard CT images. Diagnostic acceptance of vessel conspicuity was not significantly different between O-MAR images and standard CT images (p = 1.000). O-MAR images showed significantly less image noise than conventional CT images (p < .001 for both air and subcutaneous fat). Conclusion: O-MAR may be an effective solution for the metal artifacts in lower extremity CT venography; however, the distance between prostheses and vessels affects the diagnostic acceptance in patients with metallic hip or knee prostheses. Level of Evidence: Level 4, Case Series.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via decreased glucose uptake and lipogenic protein expression and increased basal lipolysis. Such an hypoxia-induced decrease in lipogenesis may be an attractive therapeutic target against lipid-associated metabolic diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

Sarcolemmal ATP-sensitive potassium (K{sub ATP}) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle K{sub ATP} channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle K{sub ATP} channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of K{sub ATP} channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish K{sub ATP} channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. - Highlights: • ATP-sensitive K{sup +} channels regulate musclin production by skeletal muscles. • Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production. • Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway. • Musclin links adipose mobilization to energy use in K{sub ATP} channel deficient skeletal muscle.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2{sup −/−} mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2{sup −/−} mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2{sup −/−} mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2{sup −/−} mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2{sup −/−} mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2{sup −/−} mice had spontaneous nonalcoholic fatty liver disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice

The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/β-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM. - Highlights: • Exposure to high-fat diet for 60 days induced prediabetes and beta cell mass expansion. • Hyperplastic pancreatic islets displayed nuclear translocation of active β-catenin. • Hyperplastic islets showed increased expression of target genes of the Wnt/β-catenin pathway. • Wnt/β-catenin pathway is activated during compensatory beta cell hyperplasia in mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Zinc alpha2 glycoprotein promotes browning in adipocytes

Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called “browning”) would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) as an important adipokine, is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase). Additionally, those effects were dramaticlly abolished by H89/SB203580, revealing ZAG-induced browning depend on PKA and p38 MAPK signaling. Overall, our findings suggest that ZAG is a candidate therapeutic agent against obesity via induction of brown fat-like phenotype in white adipocytes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Soluble dietary fiber improves energy homeostasis in obese mice by remodeling the gut microbiota

Intervention with dietary fibers is an important strategy to combat the global epidemic of obesity which is a consequence of energy imbalance. However, a possible role of the gut microbiota in effects of dietary fibers on energy homeostasis remains unclear. Here, we treated a high fat diet-induced obese (DIO) mouse model with soluble dietary fiber. Our results showed that soluble dietary fiber reduced body weight gain and the excessive accumulation of white fat tissue in DIO mice. Notably, soluble dietary fiber increased energy expenditure, but not change energy intake in DIO mice. In accordance, 16S rRNA sequencing revealed that the diversity of the gut microbiota was restored by soluble dietary fiber. Moreover, compared with controls, soluble dietary fiber resulted in a decreased ratio of Firmicutes/Bacteroidetes at the phylum level, and an increased relative abundance of the genera Roseburia at the genus level. Taken together, these findings indicate that soluble dietary fiber improves energy homeostasis and prevents obesity by increasing the diversity of the gut microbiota and the colonization of beneficial bacteria.

60 APPLIED LIFE SCIENCES↗