Kupffer Cell and Monocyte-Derived Macrophage Identification by Immunofluorescence on Formalin-Fixed, Paraffin-Embedded (FFPE) Mouse Liver Sections
Kupffer cells are the liver-resident macrophages and represent the first line of defense between the pathogens circulating from the intestines through the portal vein and systemic circulation. Recent works have highlighted the complex heterogeneity of macrophage functions and origins, thus raising awareness on the need for a better characterization of macrophage populations. The immunohistochemistry method here described, allows for a rapid distinction between Kupffer cells and monocyte-derived macrophages present on formalin-fixed, paraffin-embedded mouse liver samples. This protocol has been optimized for its reproducibility, reliability, and simplicity.
Simultaneous Inhibition of Peripheral CB1R and iNOS Mitigates Obesity-Related Dyslipidemia Through Distinct Mechanisms.
Diabetic dyslipidemia, characterized by increased plasma triglycerides and decreased HDL cholesterol levels, is a major factor contributing to nonalcoholic steatohepatitis and cardiovascular risk in type 2 diabetes. Activation of the cannabinoid-1 receptor (CB1R) and activation of inducible nitric oxide synthase (iNOS) are associated with nonalcoholic steatohepatitis progression. Here, we tested whether dual-targeting inhibition of hepatic CB1R and iNOS improves diabetic dyslipidemia in mice with diet-induced obesity (DIO mice). DIO mice were treated for 14 days with (S)-MRI-1867, a peripherally restricted hybrid inhibitor of CB1R and iNOS. (R)-MRI-1867, the CB1R-inactive stereoisomer that …
Role of the peripheral endocannabinoid system in the obesity-linked metabolic disorders genesis : Involvement of adipose tissue derived endocannabinoids.
Obesity is a pathology characterized by an excess of adipose tissue (AT) whose functions may be altered. Interestingly, strong evidence suggests that metabolic dysregulations linked to obesity is associated with an hyperactivation of the endocannabinoid system (ECS) in several organs including AT. This system, composed of cannabinoid receptors (CB1R and CB2R), their endogenous ligands (EndoCannabinoids - ECs) and their biosynthetic and degrading enzymes, is expressed both in the central nervous system and in various peripheral tissues.CB1R blockade with Rimonabant, the first antagonist marketed in 2006, has proven to be an effective therapeutic approach by reducing food intake, body mass an…