Obesity and its effects on the esophageal mucosal barrier Paris, Shere; Ekeanyanwu, Rebecca; Jiang, Yuwei ...
American journal of physiology: Gastrointestinal and liver physiology,
09/2021, Letnik:
321, Številka:
3
Journal Article
Recenzirano
Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Traditionally, these ...associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.
Perivascular adipocyte progenitor cells (APCs) can generate cold temperature-induced thermogenic beige adipocytes within white adipose tissue (WAT), an effect that could counteract excess fat mass ...and metabolic pathologies. Yet, the ability to generate beige adipocytes declines with age, creating a key challenge for their therapeutic potential. Here we show that ageing beige APCs overexpress platelet derived growth factor receptor beta (Pdgfrβ) to prevent beige adipogenesis. We show that genetically deleting Pdgfrβ, in adult male mice, restores beige adipocyte generation whereas activating Pdgfrβ in juvenile mice blocks beige fat formation. Mechanistically, we find that Stat1 phosphorylation mediates Pdgfrβ beige APC signaling to suppress IL-33 induction, which dampens immunological genes such as IL-13 and IL-5. Moreover, pharmacologically targeting Pdgfrβ signaling restores beige adipocyte development by rejuvenating the immunological niche. Thus, targeting Pdgfrβ signaling could be a strategy to restore WAT immune cell function to stimulate beige fat in adult mammals.
Building on an action-orientation perspective of power, original hypotheses regarding power and consumer switching behavior are presented. Because high power is associated with a readiness to act, ...and switching behavior often requires taking action in some form, inducing consumers to feel powerful is hypothesized to increase consumer switching. Multiple experiments provide support for this perspective along with evidence for the process via both moderation and mediation. This works contributes to the consumer switching literature by demonstrating power as a new psychological catalyst for switching behavior. This work also adds to the power literature by distinguishing between goal priming and semantic priming accounts of the action orientation of high power. Specifically, consistent with a goal priming account, engaging in action is found to sate consumers’ subsequent need for action as opposed to maintain or increase consumers’ desire to act, as might be predicted from a semantic priming account.
Thermogenic beige fat found in white adipose tissue is a potential therapeutic target to curb the global obesity and diabetes epidemic. However, these inducible thermogenic beige adipocytes have been ...thought to be short-lived and to rapidly convert to “white-like” adipocytes after discontinuing stimuli. In this study, using effective labeling techniques and genetic mouse tools, we demonstrate that a subset of UCP1+ cells that exist within white adipose tissue are able to self-divide and contribute to new beige adipocyte recruitment in response to β3 stimuli. When these cells are depleted or their adipogenic capability is blocked, β3-induced beige adipocyte formation is impaired. We also identify a cell-cycle machinery of p21 and CDKN2A as a molecular basis of beige adipocyte regulation. Collectively, our findings provide new insights into the cellular and molecular mechanisms of beige adipocyte regulation and potential therapeutic opportunities to induce the beige phenotype and treat metabolic disease.
•A subset of UCP1+ cells present in white adipose tissue generate new beige fat cells•UCP1+ cell ablation or functional disruption impairs beige adipocyte formation•Blocking division of UCP1+ cells inhibits beige adipocyte formation•Promoting division of UCP1+ cells enhances beige adipocyte formation
Park et al. demonstrate that new UCP1+ beige fat cells in the inguinal white adipose tissue arise from pre-existing UCP1+ cells in response to β3-agonist activation in a regionally selective manner in mice. Moreover, cell-cycle regulators play an important role in beige fat cell expansion in this process.
To effectively enhance the thermal security of the Li-ion battery packs used in the electric vehicle industry, novel cooling systems equipped with serpentine channels are established. Then, the heat ...generation model is established and verified experimentally. In this research study, the structure of the cooling channel, the coolant velocity, the coolant temperature, and the coolant flow direction are considered to be the influencing factors. The results demonstrate that, by adopting the serpentine cooling channel, a better thermal conductivity can be obtained, and the type-B cooling system possesses a more reasonable structure. For different types of liquid cooling systems, the coolant temperature has a small influence on the temperature nephogram; however, for the same type of system, the coolant temperature strongly influences the temperature distribution. Similarly, the temperature difference is only related to the type of cooling system, with ∼6.09 and 5.53 K obtained for the type-A and type-B cooling systems, respectively. Furthermore, allowing the coolant in the serpentine cooling channels to flow in opposite directions can lower the value of the maximum temperature and temperature difference.
Curcumin (Cur) is a phytochemical with various beneficial properties, including antioxidant, anti-inflammatory, and anticancer activities. However, its hydrophobicity, poor bioavailability, and ...stability limit its application in many biological approaches. In this study, a novel amphiphilic chitosan wall material was synthesized. The process was carried out via grafting chitosan with succinic anhydride (SA) as a hydrophilic group and deoxycholic acid (DA) as a hydrophobic group; sup.1H-NMR, FTIR, and XRD were employed to characterize the amphiphilic chitosan (CS—SA—DA). Using a low-cost, inorganic solvent-based procedure, CS—SA—DA was self-assembled to load Cur nanomicelles. This amphiphilic polymer formed self-assembled micelles with a core–shell structure and a critical micelle concentration (CMC) of 0.093 mg·mLsup.−1. Cur-loaded nanomicelles were prepared by self-assembly and characterized by the Nano Particle Size Potential Analyzer and transmission electron microscopy (TEM). The mean particle size of the spherical Cur-loaded micelles was 770 nm. The drug entrapment efficiency and loading capacities were up to 80.80 ± 0.99% and 19.02 ± 0.46%, respectively. The in vitro release profiles of curcumin from micelles showed a constant release of the active drug molecule. Cytotoxicity studies and toxicity tests for zebrafish exhibited the comparable efficacy and safety of this delivery system. Moreover, the results showed that the entrapment of curcumin in micelles improves its stability, antioxidant, and anti-inflammatory activity.
The deposition of dust and condensation of fog will block the scattering and transmission of light, thus affecting the performance of optical devices. In this work, flexible polyethylene ...terephthalate (PET) foil functionalized by active dust removal and anti-fogging characteristics is realized which combines electrodynamic screen (EDS) and electro-heating devices. In lieu of traditional measurement methods of dust removal efficiency, the PSNR is employed to characterize the dust removal efficiency of the film for the first time. The results show that both dust removal and anti-fogging improve the image quality, in which the dust removal increases the PSNR from 28.1 dB to 34.2 dB and the anti-fogging function realizes a film temperature rise of 16.7 ∘C in 5 min, reaching a maximum of 41.3 ∘C. According to the high sensitivity of the PSNR, we propose a fully automatic CIS film-driven algorithm, and its feasibility has been demonstrated.
This systematic review aims to offer an updated understanding of the relationship between omega-3 supplementation and/or vitamin D and autism spectrum disorders (ASD). The databases PubMed, Cochrane ...Library, Web of Science, EMBASE, CINAHL, Vip, CNKI, Wanfang, China Biomedical Database databases were searched using keywords, and relevant literature was hand-searched. Papers (
n
= 1,151) were systematically screened and deemed eligible since 2002. Twenty clinical controlled studies were included in the final review. The findings were analyzed for intervention effects focusing on the core symptoms of ASD, included social functioning, behavioral functioning, speech function and biomarkers changes. The review found that the effects of omega-3 supplementation on ASD were too weak to conclude that core symptoms were alleviated. Vitamin D supplementation improved core symptoms, particularly behavioral functioning, however, the results of the literatures included in this study were slightly mixed, we cannot directly conclude that vitamin D supplementation has a beneficial effect on a specific symptom of ASD, but the overall conclusion is that vitamin D supplementation has a positive effect on behavioral functioning in ASD. Omega-3 and vitamin D combination supplementation has a good combined effect on social and behavioral outcomes in patients with ASD.
Heterochromatin is a tightly packed form of chromatin that is associated with DNA methylation and histone 3 lysine 9 methylation (H3K9me). Here, we identify an H3K9me2-binding protein, Agenet domain ...(AGD)-containing p1 (AGDP1), in Arabidopsis thaliana. Here we find that AGDP1 can specifically recognize the H3K9me2 mark by its three pairs of tandem AGDs. We determine the crystal structure of the Agenet domain 1 and 2 cassette (AGD12) of Raphanus sativus AGDP1 in complex with an H3K9me2 peptide. In the complex, the histone peptide adopts a unique helical conformation. AGD12 specifically recognizes the H3K4me0 and H3K9me2 marks by hydrogen bonding and hydrophobic interactions. In addition, we find that AGDP1 is required for transcriptional silencing, non-CG DNA methylation, and H3K9 dimethylation at some loci. ChIP-seq data show that AGDP1 preferentially occupies long transposons and is associated with heterochromatin marks. Our findings suggest that, as a heterochromatin-binding protein, AGDP1 links H3K9me2 to DNA methylation in heterochromatin regions.
A potential therapeutic target to curb obesity and diabetes is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define ...the critical role of cyclin dependent kinase inhibitor 2A (Cdkn2a) as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and male mice confer long-term metabolic protection from diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistically, Cdkn2a promotes the expression and activity of beclin 1 (BECN1) by directly binding to its mRNA and its negative regulator BCL2 like 1 (BCL2L1), activating autophagy and accelerating the beige-to-white transition. Reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a ablation. Furthermore, hyperactive BECN1 alone accelerates the beige-to-white transition in mice and human. Notably, both Cdkn2a and Becn1 exhibit striking positive correlations with adiposity. Hence, blocking Cdkn2a-mediated BECN1 activity holds therapeutic potential to sustain beige adipocytes in treating obesity and related metabolic diseases.
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