Poplar Propolis Ethanolic Extract Reduces Body Weight Gain and Glucose Metabolism Disruption in High-Fat Diet-Fed Mice.

SCOPE: Current evidence supports the beneficial effect of polyphenols on the management of obesity and associated comorbidities. This is the case for propolis, a polyphenol-rich substance produced by bees. The aim of the present study is to evaluate the effect of a poplar propolis ethanolic extract (PPEE) on obesity and glucose homeostasis, and to unveil its putative molecular mechanisms of action. METHODS AND RESULTS: Male high-fat (HF) diet-fed mice are administered PPEE for 12 weeks. PPEE supplementation reduces the HF-mediated adiposity index, adipocyte hypertrophy, and body weight gain. It also improves HOMA-IR and fasting glucose levels. Gene expression profiling of adipose tissue (AT) shows an induction of mRNA related to lipid catabolism and mitochondrial biogenesis and inhibition of mRNA coding for inflammatory markers. Interestingly, several Nrf2-target genes are induced in AT following administration of PPEE. The ability of PPEE to induce the expression of Nrf2-target genes is studied in adipocytes. PPEE is found to transactivate the Nrf2 response element and the Nrf2 DNA-binding, suggesting that part of the effect of PPEE can be mediated by Nrf2. CONCLUSION: PPEE supplementation may represent an interesting preventive strategy to tackle the onset of obesity and associated metabolic disorders.

Role of systemic infection, cross contaminations and super-shedders in Salmonella carrier state in chicken.

Carriage of Salmonella is often associated with a high level of bacterial excretion and generally occurs after a short systemic infection. However, we do not know whether this systemic infection is required or whether the carrier-state corresponds to continuous reinfection or real persistence in caecal tissue. The use of a Salmonella Enteritidis bamB mutant demonstrated that a carrier-state could be obtained in chicken in the absence of systemic infection. The development of a new infection model in isolator showed that a marked decrease in animal reinfection and host-to-host transmission between chicks led to a heterogeneity of S. Enteritidis excretion and colonization contrary to what was observed in cages. This heterogeneity of infection was characterized by the presence of super-shedders, which constantly disseminated Salmonella to the low-shedder chicks, mainly through airborne movements of contaminated dust particles. The presence of super-shedders, in the absence of host-to-host transmission, demonstrated that constant reinfection was not required to induce a carrier-state. Finally, our results suggest that low-shedder chicks do not have a higher capability to destroy Salmonella but instead can block initial Salmonella colonization. This new paradigm opens new avenues to improve understanding of the carrier-state mechanisms and to define new strategies to control Salmonella infections.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Gene Expression Pattern in Response to Cholecalciferol Supplementation Highlights Cubilin as a Major Protein of 25(OH)D Uptake in Adipocytes and Male Mice White Adipose Tissue.

It is well established that the active form of vitamin D (i.e., 1,25-dihydroxyvitamin D [1,25(OH)2D]) regulates the expression of genes involved in its own metabolism and transport in the kidney and possibly in the liver. However, little is known about the transcriptional impact of cholecalciferol supplementation on white adipose tissue (WAT) and adipocytes, which are a major site of vitamin D and 25-hydroxyvitamin D [25(OH)D] storage in the organism. To fill this gap, we investigated the impact of cholecalciferol supplementation in WAT via a panel of genes coding for enzymes and proteins involved in vitamin D metabolism and uptake. Mice supplemented with cholecalciferol (15,000 IU/kg of body weight per day) for 4 days showed decreased messenger RNA (mRNA) levels of proteins involved in cholecalciferol metabolism (Cyp24a1, Cyp27a1) and decreased cubilin mRNA levels in WAT. These data were partly confirmed in 3T3-L1 adipocytes incubated with 1,25(OH)2D. The downregulation of cubilin mRNA observed in WAT and in 3T3-L1 was confirmed at the protein level in WAT and at the mRNA level in human primary adipocytes. Vitamin D receptor (VDR) agonist (EB1089) and RNA interference approaches demonstrated that VDR was involved in this regulation. Furthermore, chemical inhibitor and RNA inference analysis demonstrated that cubilin was involved in 25(OH)D uptake by adipocytes. This study established an overall snapshot of the genes regulated by cholecalciferol in mouse WAT and cell-autonomously in adipocytes. We highlighted that the regulation of cubilin expression was mediated by a VDR-dependent mechanism, and we demonstrated that cubilin was involved in 25(OH)D uptake by adipocytes.

All-trans-retinoic acid represses chemokine expression in adipocytes and adipose tissue by inhibiting NF-κB signaling.

An effect of the Vitamin A metabolite all-trans-retinoic acid (ATRA) on body weight regulation and adiposity has been described, but little is known about its impact on obesity-associated inflammation. Our objective was to evaluate the overall impact of this metabolite on inflammatory response in human and mouse adipocytes, using high-throughput methods, and to confirm its effects in a mouse model. ATRA (2 µM for 24 h) down-regulated the mRNA expression of 17 chemokines in human adipocytes, and limited macrophage migration in a TNFα-conditioned 3 T3-L1 adipocyte medium (73.7%, P<.05). These effects were confirmed in mice (n=6-9 per group) subjected to oral gavage of ATRA (5 mg/kg of body weight) and subsequently injected intraperitoneally with lipopolysaccharide. In this model, both systemic and adipose levels of inflammatory markers were reduced. The antiinflammatory effect of ATRA was associated with a reduction in the phosphorylation levels of IκB and p65 (~50%, P<.05), two subunits of the NF-κB pathway, probably mediated by PGC1α, in 3 T3-L1 adipocytes. Taken together, these results show a significant overall antiinflammatory effect of ATRA on proinflammatory cytokine and chemokine production in adipocyte and adipose tissue and suggest that ATRA supplementation may represent a strategy of preventive nutrition to fight against obesity and its complications.