Link between metformin and the peroxisome proliferator-activated receptor γ pathway in the uterine tissue of hyperandrogenized prepubertal mice

Elia, Evelin Mariel; Pustovrh, María Carolina; Amalfi, Sabrina; Devoto, L; Motta, Alicia Beatriz

doi:10.1016/j.fertnstert.2011.02.004

Cited by 17 publications

(12 citation statements)

References 38 publications

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“…This fits well to results by others showing that application of estradiol increases the 12-LOX and 15-LOX-2 expression and activity in human umbilical vascular smooth muscle cells (Somjen et al, 2016), and enhances the 12-LOX activity in rat platelets in vivo (Chang et al, 1982). Moreover, chronic hyperandrogenism decreased the protein expression of 12-LOX in prepuberal mice (Elia et al, 2011), supporting our hypothesis of a detrimental impact of androgens on the 12/ 15-LOX pathway and thus on SPM formation.…”

Section: Nosupporting

confidence: 92%

Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis

et al. 2022

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Introduction: Sex differences in inflammation are obvious and contribute to divergences in the incidence and severity of inflammation-related diseases that frequently preponderate in women. Lipid mediators (LMs), mainly produced by lipoxygenase (LOX) and cyclooxygenase (COX) pathways from polyunsaturated fatty acids (PUFAs), regulate all stages of inflammation. Experimental and clinical studies revealed sex divergences for selected LM pathways without covering the entire LM spectrum, and only few studies have addressed the respective role of sex hormones. Here, we performed the comprehensive LM profile analysis with inflammatory peritoneal exudates and plasma from male and female mice in zymosan-induced peritonitis to identify the potential sex differences in LM biosynthesis during the inflammatory response. We also addressed the impact of sex hormones by employing gonadectomy.Methods: Adult male and female CD1 mice received intraperitoneal injection of zymosan to induce peritonitis, a well-established experimental model of acute, self-resolving inflammation. Mice were gonadectomized 5 weeks prior to peritonitis induction. Peritoneal exudates and plasma were taken at 4 (peak of inflammation) and 24 h (onset of resolution) post zymosan and subjected to UPLC–MS-MS–based LM signature profiling; exudates were analyzed for LM biosynthetic proteins by Western blot; and plasma was analyzed for cytokines by ELISA.Results: Pro-inflammatory COX and 5-LOX products predominated in the peritoneum of males at 4 and 24 h post-zymosan, respectively, with slightly higher 12/15-LOX products in males after 24 h. Amounts of COX-2, 5-LOX/FLAP, and 15-LOX-1 were similar in exudates of males and females. In plasma of males, only moderate elevation of these LMs was apparent. At 4 h post-zymosan, gonadectomy strongly elevated 12/15-LOX products in the exudates of males, while in females, free PUFA and LOX products were rather impaired. In plasma, gonadectomy impaired most LMs in both sexes at 4 h with rather up-regulatory effects at 24 h. Finally, elevated 15-LOX-1 protein was evident in exudates of males at 24 h which was impaired by orchiectomy without the striking impact of gonadectomy on other enzymes in both sexes.Conclusions: Our results reveal obvious sex differences and roles of sex hormones in LM biosynthetic networks in acute self-resolving inflammation in mice, with several preponderances in males that appear under the control of androgens.

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Section: Nosupporting

confidence: 92%

Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis

et al. 2022

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“…In addition, it binds to PFK1 and FBP1 in the liver with a high affinity to modulate gluconeogenic and glycolytic enzymes independently via AMPK signaling [31][32][33]. Metformin treatment elevates the expression of pAMPK and phosphorylates pACC with an associated increase in lactate production, a decrease in glucose production, and an increase in fatty acid oxidation, indicating glucose oxidation via glycolysis [34][35][36]. Sleep deprivation-induced hyperglycemia is attenuated by metformin via the activation of GLUT2, PPARγ, pAMPK, pACC, GCK, PFK1, and FBP1, ultimately enhancing the glucose oxidation by glycolysis and increasing fatty acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

Association between Sleep Deprivation and Metformin Treatment on Pancreatic and Liver Function in Mice

Periasamy¹,

Chien²,

Hsu³

et al. 2020

OBM HG

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Metformin has been widely used as a therapeutic drug for hyperglycemia and diabetes. Sleep is a vital and restorative process that is necessary for the proper functioning of organs. Sleep deprivation can induce multi-organ injury, including damage to the pancreas and liver that may result in hyperglycemia and diabetes. We studied the role of metformin in reversing sleep deprivation-induced hyperglycemia and pancreatic and liver dysfunction in mice. Mice were kept in cages and fed water and food ad libitum. Mice were subjected to a cycle of 1-day sleep deprivation (7:00 am-7:00 pm) and 1-day sleep for 30 days (15 cycles). Metformin (100 or 300 mg/kg/day p.o.) was administered from 16th to 30th day. Animals were killed on day 31. The pancreatic function was analyzed by determining the levels of serum glucose, amylase (AMYL), and insulin. Inflammation of the pancreas and liver was investigated by studying the expression of iNOS and NFĸB, and levels of cytokines. Proteins involved in the GLUT2-PPARγ-pAMPK glycolytic pathway in the liver were analyzed to evaluate the anti-hyperglycemic role of metformin. Sleep deprivation increased blood glucose, AMYL, and GPT levels. Furthermore, it resulted in liver and pancreatic inflammation.

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“…acesulfame (Simon et al, 2013), saccharin (Simon et al, 2013), irbesartan (Afzal et al, 2016), valsartan (Hasan et al, 2014;Storka et al, 2008), diclofenac (Ayoub et al, 2009;Puhl et al, 2015), ibuprofen (Puhl et al, 2015), dibutyl phthalate (Lapinskas et al, 2005;Pereira-Fernandes et al, 2013), metformin (Elia et al, 2011); methyl paraben (Pereira-Fernandes et al, 2013); PPARα: metformin (Maida et al, 2011); dibutyl phthalate (Lapinskas et al, 2005), irbesartan (Rong et al, 2010); fenofibric acid (Qiu et al, 2017);…”

Section: Transactivation Assaysmentioning

confidence: 99%

Linking chemical exposure to lipid homeostasis: A municipal waste water treatment plant influent is obesogenic for zebrafish larvae

Barbosa

Capela

Rodolfo

et al. 2019

Ecotoxicology and Environmental Safety

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Obesity, a risk factor for the development of type-2 diabetes, hypertension, cardiovascular disease, hepatic steatosis and some cancers, has been ranked in the top 10 health risk in the world by the World Health Organization. Despite the growing body of literature evidencing an association between the obesity epidemic and specific chemical exposure across a wide range of animal taxa, very few studies assessed the effects of chemical mixtures and environmental samples on lipid homeostasis. Additionally, the mode of action of several chemicals reported to alter lipid homeostasis is still poorly understood. Aiming to fill some of these gaps, we combined an in vivo assay with the model species zebrafish (Danio rerio) to screen lipid accumulation and evaluate expression changes of key genes involved in lipid homeostasis, alongside with an in vitro transactivation assay using human and zebrafish nuclear receptors, retinoid X receptor α and peroxisome proliferator-activated receptor γ.Zebrafish larvae were exposed from 4 day post-fertilization until the end of the experiment (day 18), to six different treatments: experimental control, solvent control, tributyltin at 100 ng/L Sn and 200 ng/L Sn (positive control), and wastewater treatment plant influent at 1.25% and 2.5%. Exposure to tributyltin and to 2.5% influent led to a significant accumulation of lipids, with white adipose tissue deposits concentrating in the perivisceral area. The highest in vitro tested influent concentration (10%) was able to significantly transactivate the human heterodimer PPARγ/RXRα, thus suggesting the presence in the influent of HsPPARγ/RXRα agonists.Our results demonstrate, for the first time, the ability of complex environmental samples from a municipal waste water treatment plant influent to induce lipid accumulation in zebrafish larvae.

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Link between metformin and the peroxisome proliferator-activated receptor γ pathway in the uterine tissue of hyperandrogenized prepubertal mice

Cited by 17 publications

References 38 publications

Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis

Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis

Association between Sleep Deprivation and Metformin Treatment on Pancreatic and Liver Function in Mice

Linking chemical exposure to lipid homeostasis: A municipal waste water treatment plant influent is obesogenic for zebrafish larvae

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