scholarly journals Treatment of Overweight and Obesity by Suppressing Intestinal Epithelial Renewal in a Mouse Model of Obesity

2022 ◽  
Author(s):  
Wei-ping Zeng
Keyword(s):  
Cell Proliferation ◽  
Weight Loss ◽  
Epithelial Cells ◽  
Mouse Model ◽  
Fat Mass ◽  
Overweight And Obesity ◽  
Intestinal Epithelial ◽  
Obese Mice ◽  
Intestinal Villi ◽  
Obesity And Overweight

Abstract Obesity and overweight pose serious risk for many diseases and clinical conditions.However currently available weight loss strategies and pharmacotherapies of obesity are notsatisfactory. This study shows that treatments with pH modifiers such as acids are not only welltolerated by obese mice but also very effective in reducing bodyweight and fat mass by depletingand suppressing the proliferation of proliferating epithelial cells of the intestinal villi. Thereforeother cell proliferation inhibitors that suppress intestinal epithelial renewal can also be used forpharmacotherapy of obesity and overweight.

scholarly journals Treatment of Overweight and Obesity by Suppressing Intestinal Epithelial Renewal in a Mouse Model of Obesity

2021 ◽  
Author(s):  
Wei-ping Zeng
Keyword(s):  
Cell Proliferation ◽  
Weight Loss ◽  
Epithelial Cells ◽  
Mouse Model ◽  
Fat Mass ◽  
Overweight And Obesity ◽  
Intestinal Epithelial ◽  
Obese Mice ◽  
Obesity And Overweight ◽  
Clinical Conditions

Abstract Obesity and overweight pose serious risk for many diseases and clinical conditions. However currently available weight loss strategies and pharmacotherapies of obesity are not satisfactory. This study shows that treatments with pH modifiers such as acids are not only well tolerated by obese mice but also very effective in reducing bodyweight and fat mass by depleting and suppressing the proliferation of proliferating epithelial cells of the intestinal villi. Therefore other cell proliferation inhibitors that suppress intestinal epithelial renewal can also be used for pharmacotherapy of obesity and overweight.

scholarly journals Treatment of Overweight and Obesity by Suppressing Intestinal Epithelial Renewal in a Mouse Model of Obesity

2021 ◽  
Author(s):  
Wei-ping Zeng
Keyword(s):  
Cell Proliferation ◽  
Weight Loss ◽  
Epithelial Cells ◽  
Mouse Model ◽  
Fat Mass ◽  
Overweight And Obesity ◽  
Intestinal Epithelial ◽  
Obese Mice ◽  
Obesity And Overweight ◽  
Clinical Conditions

Abstract Obesity and overweight pose serious risk for many diseases and clinical conditions. However currently available weight loss strategies and pharmacotherapies of obesity are not satisfactory. This study shows that treatments with pH modifiers such as acids are not only well tolerated by obese mice but also very effective in reducing bodyweight and fat mass by depleting and suppressing the proliferation of proliferating epithelial cells of the intestinal villi. Therefore other cell proliferation inhibitors that suppress intestinal epithelial renewal can also be used for pharmacotherapy of obesity and overweight.

scholarly journals The transcription factor FoxM1 activates Nurr1 to promote intestinal regeneration after ischemia/reperfusion injury

2019 ◽  
Vol 51 (11) ◽  
pp. 1-12 ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Tingting Zhou ◽  
Ningwei Che ◽  
Baiying Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Intestinal Mucosa ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Epithelial ◽  
Ki 67 ◽  
Intestinal Regeneration ◽  
Foxm1 Expression ◽  
Intestinal Ischemia Reperfusion

Abstract FoxM1 is involved in the regeneration of several organs after injury and expressed in the intestinal mucosa. The intrinsic mechanism of FoxM1 activity in the mucosa after intestinal ischemia/reperfusion (I/R) injury has not been reported. Therefore, we investigated the role of FoxM1 in mediating intestinal mucosa regeneration after I/R injury. Expression of FoxM1 and the proliferation of intestinal mucosa epithelial cells were examined in rats with intestinal I/R injury and an IEC-6 cell hypoxia/reperfusion (H/R) model. The effects of FoxM1 inhibition or activation on intestinal epithelial cell proliferation were measured. FoxM1 expression was consistent with the proliferation of intestinal epithelial cells in the intestinal mucosa after I/R injury. Inhibition of FoxM1 expression led to the downregulation of Ki-67 expression mediated by the inhibited expression of Nurr1, and FoxM1 overexpression promoted IEC-6 cell proliferation after H/R injury through activating Nurr1 expression. Furthermore, FoxM1 directly promoted the transcription of Nurr1 by directly binding the promoter of Nurr1. Further investigation showed low expression levels of FoxM1, Nurr1, and Ki-67 in the intestinal epithelium of patients with intestinal ischemic injury. FoxM1 acts as a critical regulator of intestinal regeneration after I/R injury by directly promoting the transcription of Nurr1. The FoxM1/Nurr1 signaling pathway represents a promising therapeutic target for intestinal I/R injury and related clinical diseases.

Induction of endothelin-1 synthesis by IL-2 and its modulation of rat intestinal epithelial cell growth

1998 ◽  
Vol 275 (3) ◽  
pp. G556-G563 ◽  
Author(s):  
Takeharu Shigematsu ◽  
Soichiro Miura ◽  
Masahiko Hirokawa ◽  
Ryota Hokari ◽  
Hajime Higuchi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Proliferative Response ◽  
Intestinal Epithelial Cell ◽  
Culture Media ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

Endothelin (ET), a vasoconstrictive peptide, is known to have a variety of biological actions. Although ET is released by vascular endothelial cells, other cell populations also have been reported to synthesize and release ET. In this study, we examined whether ET is synthesized by intestinal epithelial cells and whether it affects induction of epithelial cell proliferation by interleukin-2 (IL-2). Subconfluent monolayers of intestinal epithelial cells (IEC-6 and IEC-18) were maintained in serum-free medium before addition of rat IL-2. Both IEC-6 and IEC-18 cells released ET-1 into the medium under unstimulated conditions, as determined by a sandwich ELISA. IL-2 significantly enhanced ET-1 release in a time-dependent manner. ET-3 was not detectable in the culture media of either cell line. Expression of ET-1 and ET-3 mRNA in epithelial cells was assessed by competitive PCR. Both cell lines were shown to express ET-1 mRNA, but no ET-3 mRNA was detected. IL-2 treatment enhanced ET-1 mRNA expression by both IEC-6 and IEC-18 cells. Both cell lines also expressed mRNA for ETA and ETB receptor subtypes. When cell proliferation was assessed, exogenous ET-1 induced a slight proliferative response in both types of cells that was consistent and significant at low ET-1 concentrations; cell growth was inhibited at a higher concentration (10−7M). IL-2 produced a significant proliferative response in both cell lines. However, the addition of ET-1 (10−7 M) to culture media attenuated the IL-2-induced increase in cell proliferation. ETA-receptor antagonists significantly enhanced cellular proliferation, suggesting involvement of the ETA receptor in modulation of IL-2-induced intestinal epithelial cell growth.

scholarly journals Human intestinal epithelial cell-induced CD8+ T cell activation is mediated through CD8 and the activation of CD8-associated p56lck.

1995 ◽  
Vol 182 (4) ◽  
pp. 1079-1088 ◽  
Author(s):  
Y Li ◽  
X Y Yio ◽  
L Mayer
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Intestinal Epithelial Cells ◽  
T Cell Proliferation ◽  
Intestinal Epithelial

The activation of CD8+ suppressor T cells by normal intestinal epithelial cells in antigen-specific or allogeneic mixed cell culture systems has significant implications for the regulation of mucosal immune responses. In this study, we found that the capacity of epithelial cells to induce CD8+ suppressor T cell activation appeared to be linked to the binding of CD8 molecules on the T cell surface. This appears to be mediated by a non-class I molecule expressed on the epithelial cell surface, which binds to CD8 and results in the activation of the CD8-associated src-like tyrosine kinase, p56lck. Epithelial cell-stimulated p56lck activation is an early event (in contrast to monocytes) and is essential for T cell activation, since proliferation could be completely abrogated by pretreatment of T cells with genestein or herbamycin, both of which are protein tyrosine kinase inhibitors. Pretreatment of T cells with anti-CD8 or of intestinal epithelial cells with an anti-epithelial cell mAb B9 inhibited p56lck activation and further confirmed that CD8 on the T cell and a CD8 ligand on the epithelial cell were involved in this T cell activation event. The specificity of this reaction was confirmed in experiments in which murine transfectants 3G4 and 3G8, expressing CD4 or CD8, respectively, were used. Coculture of 3G8 with epithelial cells but not with monocytes activated p56lck in this cell line, whereas p56lck was preferentially activated in 3G4 cells when monocytes were used as the stimulator cells. Although stimulation through CD8- and CD8-associated p56lck was important for epithelial cell-induced T cell activation, T cell proliferation could not be induced by cross-linking CD8 alone with monoclonal antibody anti-CD8. These data suggest that a second signal, possibly through the T cell antigen receptor since activation of the T cell receptor-associated kinase fyn was also seen, is required for epithelial cell-driven T cell proliferation.

scholarly journals JunD enhances miR-29b levels transcriptionally and posttranscriptionally to inhibit proliferation of intestinal epithelial cells

2015 ◽  
Vol 308 (10) ◽  
pp. C813-C824 ◽  
Author(s):  
Tongtong Zou ◽  
Jaladanki N. Rao ◽  
Lan Liu ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Intestinal Epithelial Cells ◽  
Inhibitory Effect ◽  
Microrna Expression ◽  
Intestinal Epithelial ◽  
Gut Epithelium

Through its actions as component of the activating protein-1 (AP-1) transcription factor, JunD potently represses cell proliferation. Here we report a novel function of JunD in the regulation of microRNA expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically increased the expression of primary and mature forms of miR-29b, whereas JunD silencing inhibited miR-29b expression. JunD directly interacted with the miR-29b1 promoter via AP-1-binding sites, whereas mutation of AP-1 sites from the miR-29b1 promoter prevented JunD-mediated transcriptional activation of the miR-29b1 gene. JunD also enhanced formation of the Drosha microprocessor complex, thus further promoting miR-29b biogenesis. Cellular polyamines were found to regulate miR-29b expression by altering JunD abundance, since the increase in miR-29b expression levels in polyamine-deficient cells was abolished by JunD silencing. In addition, miR-29b silencing prevented JunD-induced repression of IEC proliferation. Our findings indicate that JunD activates miR-29b by enhancing its transcription and processing, which contribute to the inhibitory effect of JunD on IEC growth and maintenance of gut epithelium homeostasis.

scholarly journals COMPOSITIONAL COMPOSITION OF THE BODY IN OBESE CHILDREN AND ADOLESCENTS

2019 ◽  
Vol 6 (1) ◽  
pp. 51-57 ◽  
Author(s):  
O. A. Gerasimchik ◽  
Ya. V. Girsh
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fat Mass ◽  
Dynamic Control ◽  
Overweight And Obesity ◽  
The Body ◽  
Excess Body Weight ◽  
Sequential Effects ◽  
Normal Body ◽  
Normal Body Weight

Background. The steady growth of obesity in the children’s age group determines the need for integrated modern approaches to diagnosis and therapy.Objective. To determine the body composition of adolescents with different body mass for the quantitative analysis of the internal environment of the organism using the method bioimpendancemetria.Design and methods. To determine the composition of the body, 121 adolescents aged 10–17 years were examined, the average age was 13.9 years (± 2.1). Evaluation of anthropometric data and determination of BMI at the 1st stage of the study allowed to identify 3 groups of patients: group 1 — adolescents with normal body weight, 40 people (33 %), group 2 — overweight, 48 people (40 %) and group 3 — obese, 33 adolescents (27 %). At stage 2nd, the analysis of the body structure using computer impedance, which allows to determine the composition of the body in a percentage.Results. When assessing the structure of the body, in group with normal body weight, the content of adipose tissue corresponds to the normal value. In adolescents overweight and obesity in 100 % of cases there was an increased content of fat mass. In the group of adolescents with normal body weight, the percentage deviation of AKM is 16–17 %, in the group with excess body weight 12–40 %. Insufficient as well as excessive percentage of AKM causes hunger. The higher AKM in full adolescents, the more difficult the process of weight loss. During the evaluation of the main metabolism it was found that in the group of obese patients the indicators exceeded those in the groups with normal and overweight.Conclusion. The use of bioimpedance analysis allows to create an optimal set of sequential effects aimed at correcting the fat mass, water composition and muscle mass of the patient, which determines a more directed and effective weight loss and the possibility of dynamic control.

scholarly journals A Self-Directed Mobile Intervention (WaznApp) to Promote Weight Control Among Employees at a Lebanese University: Protocol for a Feasibility Pilot Randomized Controlled Trial (Preprint)

2018 ◽  
Author(s):  
Marco Bardus ◽  
Ghassan Hamadeh ◽  
Bouchra Hayek ◽  
Rawan Al Kherfan
Keyword(s):  
Weight Loss ◽  
Randomized Controlled Trial ◽  
Weight Management ◽  
Weight Control ◽  
Mobile Apps ◽  
Controlled Trial ◽  
Overweight And Obesity ◽  
Randomized Controlled ◽  
Obesity And Overweight ◽  
And Control

BACKGROUND Overweight and obesity have become major health problems globally with more than 1.9 billion overweight adults. In Lebanon, the prevalence of obesity and overweight is 65.4% combined. Risk factors of obesity and overweight are preventable and can be addressed by modifications in the environment and in an individual’s lifestyle. Mobile technologies are increasingly used in behavioral, self-directed weight management interventions, providing users with additional opportunities to attain weight control (weight loss, weight gain prevention, etc). Mobile apps may allow for the delivery of Just-in-Time Adaptive Interventions (JITAIs), which provide support through skill building, emotional support, and instrumental support, following the participants’ progress. A few commercially available apps offer JITAI features, but no studies have tested their efficacy. OBJECTIVE The primary objective of this study is to examine the feasibility of a self-directed weight loss intervention, targeting employees of an academic institution, using a virtual coaching app with JITAI features (Lark) and a self-help calorie-counting app (MyFitnessPal). The secondary objective is to estimate the effects of the intervention on main study outcomes. METHODS This study is a single-center, parallel, randomized controlled trial with 2 study arms (intervention and control). Participants will be randomly allocated in equal proportions to the intervention (Lark) and control groups (MyFitnessPal). To be eligible for this study, participants must be employed full- or part-time at the university or its medical center, able to read English, have a smartphone, and be interested in controlling their weight. Recruitment strategies entail email invitations, printed posters, and social media postings. We will assess quantitative rates of recruitment, adherence, and retention, self-reported app quality using the user version of the Mobile App Rating Scale. We will also assess changes in weight-related outcomes (absolute weight and waist circumference), behavioral outcomes (physical activity and diet), and cognitive factors (motivation to participate in the trial and to manage weight). RESULTS WaznApp was funded in June 2017, and recruitment started in March 2018. CONCLUSIONS This study will provide information as to whether the selected mobile apps offer a feasible solution for promoting weight management in an academic workplace. The results will inform a larger trial whose results might be replicated in similar workplaces in Lebanon and the Middle East and North Africa region, and will be used as a benchmark for further investigations in other settings and similar target groups. CLINICALTRIAL ClinicalTrials.gov NCT03321331; https://clinicaltrials.gov/ct2/show/NCT03321331 (Archived by WebCite at http://www.webcitation.org/6ys9NOLo5) REGISTERED REPORT IDENTIFIER RR1-10.2196/9793

Obese Adipose Tissue Modulates Pro-inflammatory Responses of Mouse Airway Epithelial Cells

2021 ◽  
Author(s):  
Jennifer L Ather ◽  
Katherine E Van Der Vliet ◽  
Madeleine M Mank ◽  
Leah F Reed ◽  
Anne E Dixon ◽  
...  
Keyword(s):  
Weight Loss ◽  
Epithelial Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet

Although recognized as an important endocrine organ, little is known about the mechanisms through which adipose tissue can regulate inflammatory responses in distant tissues, such as lung, that are affected by obesity. To explore potential mechanisms, male C57BL/6J mice were provided either high-fat diet, low-fat diet, or were provided a high-fat diet then switched to the low-fat diet to promote weight loss. Visceral adipocytes were then cultured in vitro to generate conditioned media (CM) that was used to treat both primary (MTEC) and immortalized (MTCC) airway epithelial cells. Adiponectin levels were greatly depressed in the CM from both obese and diet-switched adipocytes relative to mice continually fed the low-fat diet. MTEC from obese mice secreted higher baseline levels of inflammatory cytokines than MTEC from lean or diet-switched mice. MTEC treated with obese adipocyte CM increased their secretion of these cytokines compared to MTEC treated with lean CM. Diet-switched CM modestly decreased the production of cytokines compared to obese CM, and these effects were recapitulated when the CM was used to treat MTCC. Adipose stromal vascular cells from obese mice expressed genes consistent with an M1 macrophage phenotype and decreased eosinophil abundance compared to lean SVF, a profile that persisted in the lean diet-switched mice despite substantial weight loss. Soluble factors secreted from obese adipocytes exert a pro-inflammatory effect on airway epithelial cells, and these alterations are attenuated by diet-induced weight loss, which could have implications for the airway dysfunction related to obese asthma and its mitigation by weight loss.

scholarly journals SOX9 directly regulates IGFBP-4 in the intestinal epithelium

2013 ◽  
Vol 305 (1) ◽  
pp. G74-G83 ◽  
Author(s):  
Zhongcheng Shi ◽  
Chi-I Chiang ◽  
Toni-Ann Mistretta ◽  
Angela Major ◽  
Yuko Mori-Akiyama
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Target Genes ◽  
Intestinal Epithelial Cells ◽  
Neutralizing Antibody ◽  
Intestinal Epithelial ◽  
Loss Of Function ◽  
Deficient Mice

SOX9 regulates cell lineage specification by directly regulating target genes in a discrete number of tissues, and previous reports have shown cell proliferative and suppressive roles for SOX9. Although SOX9 is expressed in colorectal cancer, only a few direct targets have been identified in intestinal epithelial cells. We previously demonstrated increased proliferation in Sox9-deficient crypts through loss-of-function studies, indicating that SOX9 suppresses cell proliferation. In this study, crypt epithelial cells isolated from Sox9-deficient mice were used to identify potential target genes of SOX9. Insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4), an inhibitor of the IGF/IGF receptor pathway, was significantly downregulated in Sox9-deficient intestinal epithelial cells and adenoma cells of Sox9-deficient Apc Min/+ mice. Immunolocalization experiments revealed that IGFBP-4 colocalized with SOX9 in mouse and human intestinal epithelial cells and in specimens from patients with primary colorectal cancer. Reporter assays and chromatin immunoprecipitation demonstrated direct binding of SOX9 to the IGFBP-4 promoter. Overexpression of SOX9 attenuated cell proliferation, which was restored following treatment with a neutralizing antibody against IGFBP-4. These results suggest that SOX9 regulates cell proliferation, at least in part via IGFBP-4. Furthermore, the antiproliferative effect of SOX9 was confirmed in vivo using Sox9-deficient mice, which showed increased tumor burden when bred with Apc Min/+ mice. Our results demonstrate, for the first time, that SOX9 is a transcriptional regulator of IGFBP-4 and that SOX9-induced activation of IGFBP-4 may be one of the mechanisms by which SOX9 suppresses cell proliferation and progression of colon cancer.

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