AMPK in regulation of apical junctions and barrier function of intestinal epithelium

Zhu, Mei‐Jun; Sun, Xiaofei; Du, Min

doi:10.1080/21688370.2018.1487249

Cited by 56 publications

(53 citation statements)

References 121 publications

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“…; Zhu et al . ). In addition, a negative correlation of placental AMPK phosphorylation in relation to body mass index and birth weight was reported (Jansson et al .…”

Section: Resultsmentioning

confidence: 97%

Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth

Son

Liu

Tian

et al. 2019

The Journal of Physiology

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Key pointsr Maternal exercise improves the metabolic health of maternal mice challenged with a high-fat diet.r Exercise intervention of obese mothers prevents fetal overgrowth. r Exercise intervention reverses impaired placental vascularization in obese mice. r Maternal exercise activates placental AMP-activated protein kinase, which was inhibited as a result of maternal obesity.Abstract More than one-third of pregnant women in the USA are obese and maternal obesity (MO) negatively affects fetal development, which predisposes offspring to metabolic diseases. The placenta mediates nutrient delivery to fetuses and its function is impaired as a result of MO. Exercise ameliorates metabolic dysfunction resulting from obesity, although its effect on placental function of obese mothers has not been explored. In the present study, C57BL/6J female mice were randomly assigned into two groups fed either a control or a high-fat diet (HFD) and then the mice on each diet were further divided into two subgroups with/without exercise. In HFD-induced obese mice, daily treadmill exercise during pregnancy reduced body weight gain, lowered serum glucose and lipid concentration, and improved insulin sensitivity of maternal mice. Importantly, maternal exercise prevented fetal overgrowth (macrosomia) induced by MO. To further examine the preventive effects of exercise on fetal overgrowth, placental vascularization and nutrient transporters were analysed. Vascular density and the expression of vasculogenic factors were reduced as a result of MO but were recovered by maternal exercise. On the other hand, the contents of nutrient transporters were not substantially altered by MO or exercise, suggesting that the protective effects of exercise in MO-induced fetal overgrowth were primarily a result of the alteration of placental vascularization and improved maternal metabolism. Furthermore, exercise enhanced downstream insulin signalling and activated AMP-activated protein kinase in HFD placenta. In sum, maternal exercise prevented fetal overgrowth induced by MO, which was Jun Seok Son received MS Degree in Kinesiology from Seoul National University. Currently, Jun Seok is a PhD student in the . His research interests focus on the impacts of maternal obesity, exercise, nutrition and other physiological conditions on fetal development and offspring health, especially the epigenetic mechanisms linking nutrients/metabolites to progenitor cell differentiation into myocytes/adipocytes. Ultimately, he aims to translate his work into clinical practice with respect to improving health outcomes for mothers and children affected by obesity.

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“…; Zhu et al . ). In addition, a negative correlation of placental AMPK phosphorylation in relation to body mass index and birth weight was reported (Jansson et al .…”

Section: Resultsmentioning

confidence: 97%

Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth

Son

Liu

Tian

et al. 2019

The Journal of Physiology

Self Cite

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“…Finally, we were not able to describe the detailed mechanisms of action of glutamine on colonic barrier function. Recently, AMPK activation has been reported to enhance enterocytes polarization and ameliorate the assembly of tight junction proteins, leading to an improvement of intestinal barrier function [66], probably through the AMPK–CDX2 pathway [67]. The role of AMPK in the regulation of gut barrier function in ABA mice and its modulation by glutamine requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

et al. 2019

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Background: During activity-based anorexia (ABA) in mice, enhanced paracellular permeability and reduced protein synthesis have been shown in the colon while the gut–brain axis has received increasing attention in the regulation of intestinal and mood disorders that frequently occur during anorexia nervosa, a severe eating disorder for which there is no specific treatment. In the present study, we assessed the effects of oral glutamine (Gln) or branched-chain amino acids (BCAA) supplementation during ABA to target intestinal functions, body composition and feeding behavior. Methods: C57BL/6 male mice were randomized in Control (CTRL) and ABA groups. After ABA induction, mice received, or not, either 1% Gln or 2.5% BCAA (Leu, Ile, Val) for one week in drinking water. Results: Neither Gln nor BCAA supplementation affected body weight and body composition, while only Gln supplementation slightly increased food intake. ABA mice exhibited increased paracellular permeability and reduced protein synthesis in the colonic mucosa. Oral Gln restored colonic paracellular permeability and protein synthesis and increased the mucin-2 mRNA level, whereas BCAA did not affect colonic parameters. Conclusion: In conclusion, oral Gln specifically improves colonic response during ABA. These data should be further confirmed in AN patients.

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“…AMP-activated protein kinase (AMPK), a highly conserved serine/threonine kinase, is widely known as a regulator of energy homeostasis to promote ATP generation and energy restoration [21]. When the overall energy level in a cell deceases because of increased demands by various stimulates, AMPK is activated through phosphorylation by upstream kinases or directly triggered by an elevated AMP/ ATP ratio [38]. Under heat stress, AMPK phosphorylation is downregulated in HeLa and HEK293 cells [39].…”

Section: Itemsmentioning

confidence: 99%

“…Accumulating studies have shown that activation of AMPK by pharmacological or nutraceutical approaches strengthens the epithelial barrier function [21,24,38]. AICAR treatment enhances the barrier function in Caco-2 cells [42].…”

Section: Itemsmentioning

confidence: 99%

l-Arginine alleviates heat stress-induced intestinal epithelial barrier damage by promoting expression of tight junction proteins via the AMPK pathway

et al. 2019

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Heat stress (HS) and secondary restricted blood flow to the intestines cause dysfunction of the intestinal epithelial barrier. Tight junctions (TJs) are essential to maintain intestinal integrity. l-Arginine has beneficial effects on gut functions. However, the underlying mechanisms remain largely unknown. This study tested the hypothesis that l-arginine regulates the TJ network by activating AMP-activated protein kinase (AMPK) signaling, which in turn improves intestinal barrier functions under HS. IEC-6 cells and rat small intestines were used as experiment models of heat stress. AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively. Cell proliferation, apoptosis, differential gene expression and KEGG pathway analysis, intestinal paracellular permeability, intestinal morphology, and expression of HSP and TJ proteins, and p-AMPK were determined. l-Arginine promoted cell proliferation and reduced apoptosis after heat exposure at an optimal concentration of 5 mmol. Transcriptome sequencing analysis revealed that differentially expressed genes associated with the HSP family and TJs were elevated by l-arginine. According to KEGG pathway analysis, l-arginine activated the AMPK signaling pathway. In vivo, intestinal damage resulted in obvious morphological changes as well as apoptosis with TUNEL and caspase-3 staining under HS and dorsomorphin treatments. Furthermore, HS and dorsomorphin increased the serum D-lactate concentration, diamine oxidase activity, and mRNA expression level of MLCK (P < 0.05). In contrast, l-arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia. l-Arginine had the same effect as AICAR both in vitro and in vivo, namely increasing p-AMPK protein expression. l-Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK (P < 0.05). The protein expression levels of TJ proteins ZO-1 and claudin-1 were suppressed by heat stroke and dorsomorphin, but enhanced by l-arginine and AICAR. Our findings indicate that activation of AMPK signaling by l-arginine is associated with improved intestinal mucosal barrier functions by enhancing the expression of TJs in rat small intestines and IEC-6 cells during HS.

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AMPK in regulation of apical junctions and barrier function of intestinal epithelium

Cited by 56 publications

References 121 publications

Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth

Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth

Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

l-Arginine alleviates heat stress-induced intestinal epithelial barrier damage by promoting expression of tight junction proteins via the AMPK pathway

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