scholarly journals PACAP ameliorates the fertility of obese mice through PAC1/PKA/ERK/Nrf2 signal axis

2021 ◽  
Author(s):  
Wailan Shan ◽  
Shiyin Lu ◽  
Biqian Ou ◽  
Jia Feng ◽  
Zixian Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Inflammatory Response ◽  
Male Infertility ◽  
Cell Model ◽  
Male Reproduction ◽  
Obese Mice ◽  
High Fat ◽  
Pac1 Receptor

Obesity is strongly linked to male infertility. Apoptotic inflammatory response caused by oxidative stress in testicular spermatogenic cells is one of the important causes of obesity-related male infertility. Pituitary adenylate cyclase activating polypeptide (PACAP) as a bioactive peptide secreted by the pituitary gland, has a powerful triple role of anti-oxidation, anti-apoptosis and anti-inflammation, and is involved in male reproduction regulation, but the specific mechanism remains unknown. The purpose of the current study is to explore the role of PACAP in obesity-related male infertility. In cell-level experiments, Mouse spermatocytes (GC-2) were treated with palmitate (PA) to establish an high-fat injury cell model in vitro and then treated with PACAP. In animal-level experiments, C57BL/6 male mice were fed with a high-fat diet (HFD) to induce obesity and then treated with PACAP. The cell mechanism studies showed that PACAP selectively binds to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-2) oxidative damage and apoptotic inflammatory response via the PKA/ERK/Nrf2 signaling axis. However, this mechanism was inhibited in GC-2 cells inhibiting the activity of Nrf2. The animal experiment studies showed that PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo. Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology and sperm parameters via Keap1/Nrf2/ARE pathway. These beneficial effects of PACAP were abolished in obese mice with testis-specific knockdown of Nrf2.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

scholarly journals 7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet

2018 ◽  
Vol 120 (7) ◽  
pp. 751-762 ◽  
Author(s):  
Giorgio Biasiotto ◽  
Isabella Zanella ◽  
Federica Predolini ◽  
Ivonne Archetti ◽  
Moris Cadei ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
High Fat Diet ◽  
Sugar Metabolism ◽  
Lipid Uptake ◽  
High Fat ◽  
Total Extract ◽  
The Metabolic Syndrome ◽  
Metabolic Genes

Abstract7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the correspondingPicea abiesextract (total extractP. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genesPPARγ,C/EBPαandaP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptakein vitro.

scholarly journals MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

scholarly journals CaMKIV limits metabolic damage through induction of hepatic autophagy by CREB in obese mice

2020 ◽  
Vol 244 (2) ◽  
pp. 353-367 ◽  
Author(s):  
Jiali Liu ◽  
Yue Li ◽  
Xiaoyan Zhou ◽  
Xi Zhang ◽  
Hao Meng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Inflammatory Response ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Insulin Action ◽  
Hepatic Insulin Resistance ◽  
Obese Mice ◽  
High Fat ◽  
Impaired Insulin

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice

2016 ◽  
Vol 110 ◽  
pp. 165-174 ◽  
Author(s):  
Ghazaul Dezfuli ◽  
Kenneth J. Kellar ◽  
Kenneth L. Dretchen ◽  
Yousef Tizabi ◽  
Niaz Sahibzada ◽  
...  
Keyword(s):  
Body Weight ◽  
Obese Mice

Abstract 404: NLR Family, Pyrin Domain-containing 3 Knockout Rescues Cardiac Dysfunction Induced by High-fat Diet Feeding

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Matthew R Peterson ◽  
Samantha Haller ◽  
Tracy Ta ◽  
Luiza Bosch ◽  
Aspen Smith ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Inflammatory Response ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Left Ventricular ◽  
Normal Diet ◽  
High Fat ◽  
Pyrin Domain

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.

Role of glycine-containing oligopeptides in blood cells aggregation stimulated by adrenaline

2017 ◽  
Author(s):  
М. Голубева
Keyword(s):  
Body Weight ◽  
Platelet Aggregation ◽  
Blood Cells ◽  
Regulatory Peptides ◽  
Pituitary Hormones ◽  
New Drugs ◽  
Male Rats ◽  
Current Interest

Введение. Изменение реологических свойств крови характерно для различных заболеваний, многие из которых связаны с нарушением реологии и, прежде всего, с изменением агрегации эритроцитов. Целью исследования было сравнение влияния малых регуляторных пептидов, являющихся фрагментами нейрогормонов, на агрегацию эритроцитов и тромбоцитов под действием адреналина в экспериментах in vitro. Материалы и методы. Эксперименты проводили на белых беспородных крысах-самцах, массой тела 180-200 г. Использовали пептиды, представляющие собой С-концевые фрагменты вазопрессина (Pro-Arg-Gly-NH2) и окситоцина (Pro-Leu-Gly-NH2). Результаты. Показано, что малые регуляторные пептиды, являющиеся продуктами протеолиза нейропептидов, оказывают существенное влияние на агрегатное состояние клеток крови. При сравнении влияния пептидов на агрегацию клеток крови, стимулированную адреналином, установлено, что фрагмент вазопрессина Pro-Arg-Gly-NH2 вызывал достоверное усиление агрегации как эритроцитов, так и тромбоцитов; тогда как фрагмент окситоцина Pro-Leu-Gly-NH2 ингибировал только агрегацию эритроцитов, не изменяя агрегации тромбоцитов. Заключение. Изучение путей поэтапного протеолиза пептидов может привести к разработке новых препаратов для направленной коррекции различных нарушений в организме, поэтому изучение эффектов С-концевых фрагментов гипофизарных гормонов на гемостаз является актуальным. Introduction. The changing of blood rheological properties is typical for various diseases; many of them are associated with rheology disorder and primarily with change of erythrocytes aggregation. The aim was to compare the effect of small regulatory peptides (fragments of neurohormones) on the aggregation of erythrocytes and platelets under adrenaline action in experiments in vitro. Materials and methods. Experiments were conducted on white outbred male rats, body weight 180-200 g. We used 2 peptides – C-terminal fragments of vasopressin (Pro-Arg-Gly-NH2) and oxytocin (Pro-Leu-Gly-NH2). Results. It was shown that small regulatory peptides (they are products of neuropeptides proteolysis) had a significant effect on blood cells aggregation. We compared the peptides effect on blood cells aggregation stimulated by adrenaline. It was found that vasopressin fragment Pro-Arg-Gly-NH2 significantly increased both erythrocytes and platelets aggregation, while oxytocin fragment Pro-Leu-Gly-NH2 inhibited only erythrocytes aggregation without changing of platelet aggregation. Conclusion. Investigation of phased peptides proteolysis may result in the development of new drugs for targeted correction of various disturbances. So it is of current interest to study the effects of C-terminal fragments of pituitary hormones on hemostasis.

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