Placental colonization by Fusobacterium nucleatum is mediated by binding of the Fap2 lectin to placentally displayed Gal-GalNAc.

While the existence of an indigenous placental microbiota remains controversial, several pathogens are known to be involved in adverse pregnancy outcomes. Fusobacterium nucleatum is an oral bacterium that is one of several bacteria associated with preterm birth. Oral fusobacteria translocate to the placenta hematogenously; however, the mechanisms localizing them to the placenta remain unclear.

Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis.

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CBR) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively.

Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent.

Objective: The endocannabinoid (eCB) system is increasingly recognized as being crucially important in obesity-related hepatic steatosis. By activating the hepatic cannabinoid-1 receptor (CBR), eCBs modulate lipogenesis and fatty acid oxidation. However, the underlying molecular mechanisms are largely unknown.

Dual inhibition of cannabinoid CB receptor and inducible NOS attenuates obesity-induced chronic kidney disease.

Background And Purpose: Obesity, an important risk factor for developing chronic kidney disease (CKD), affects the kidneys by two main molecular signalling pathways: the endocannabinoid/CB receptor system, whose activation in obesity promotes renal inflammation, fibrosis, and injury, and the inducible NOS (iNOS), which generates ROS resulting in oxidative stress. Hence, a compound that inhibits both peripheral CB receptors and iNOS may serve as an effective therapeutic agent against obesity-induced CKD.

Experimental Approach: Here, we describe the effect of a novel peripherally restricted, orally bioavailable dual CB receptor/iNOS antagonist, MRI-1867 (3 mg·kg ), in ameliorating obesity-induced CKD, and compared its metabolic and renal efficacies to a stand-alone peripheral CB receptor antagonist (JD5037; 3 mg·kg ), iNOS antagonist (1400W; 10 mg·kg ), and pair feeding.

WWOX somatic ablation in skeletal muscles alters glucose metabolism.

Objective: WWOX, a well-established tumor suppressor, is frequently lost in cancer and plays important roles in DNA damage response and cellular metabolism.

Methods: We re-analyzed several genome-wide association studies (GWAS) using the Type 2 Diabetes Knowledge Portal website to uncover WWOX's association with metabolic syndrome (MetS). Using several engineered mouse models, we studied the effect of somatic WWOX loss on glucose homeostasis.

Cannabinoid-1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells.

Aims: To evaluate the specific role of the endocannabinoid/cannabinoid type-1 (CB R) system in modulating mitochondrial dynamics in the metabolically active renal proximal tubular cells (RPTCs).

Materials And Methods: We utilized mitochondrially-targeted GFP in live cells (wild-type and null for the CB R) and electron microscopy in kidney sections of RPTC-CB R mice and their littermate controls. In both in vitro and in vivo conditions, we assessed the ability of CB R agonism or fatty acid flux to modulate mitochondrial architecture and function.

The therapeutic potential of targeting the peripheral endocannabinoid/CB receptor system.

Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CBR and CBR, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CBR system in modulating the metabolism in several peripheral organs.

Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic Nephropathy.

Altered glucose reabsorption the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CBR), which contributes to the development of diabetic nephropathy (DN). However, the link between CBR and GLUT2 remains to be determined.

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CBR) induces nephropathy, whereas CBR blockade improves kidney function. Whether these effects are mediated a specific cell type within the kidney remains unknown.

Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

Background & Aims: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis.

miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression.

Objective: Both non-alcoholic fatty liver disease (NAFLD) and the multitarget complexity of microRNA (miR) suppression have recently raised much interest, but the in vivo impact and context-dependence of hepatic miR-target interactions are incompletely understood. Assessing the relative in vivo contributions of specific targets to miR-mediated phenotypes is pivotal for investigating metabolic processes.

Design: We quantified fatty liver parameters and the levels of miR-132 and its targets in novel transgenic mice overexpressing miR-132, in liver tissues from patients with NAFLD, and in diverse mouse models of hepatic steatosis.

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader-Willi syndrome.

Objective: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CBR) blockade reverses obesity both in animals and humans. The first-in-class CBR antagonist rimonabant proved effective in inducing weight loss in adults with PWS.

Effects of valproic acid on the placental barrier in the pregnant mouse: Optical imaging and transporter expression studies.

Our aim was to evaluate the effects of valproic acid (VPA) on the function of the placental barrier in vivo, in pregnant mice. Studies were conducted on gestational days 12.5 (mid-gestation) or 17.