SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase

Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NA

Inhibition of chylomicron assembly leads to dissociation of hepatic steatosis from inflammation and fibrosis

Regulating dietary fat absorption may impact progression of nonalcoholic fatty liver disease (NAFLD). Here we asked if inducible inhibition of chylomicron assembly, as observed in intestine-specific microsomal triglyceride transfer protein knockout mice (Mttp-IKO), could retard NAFLD progression and/or reverse established fibrosis in two dietary models. Mttp-IKO mice fed a methionine/choline deficient (MCD) diet exhibited reduced hepatic triglycerides (TG), inflammation and fibrosis, associated with reduced oxidative stress and downstream activation of JNK and NFκB signaling pathways. However, when Mtt

The tetraspanin transmembrane protein CD53 mediates dyslipidemia and integrates inflammatory and metabolic signaling in hepatocytes

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction in fat- and fructose-exposed contexts. Furthermore, germline CD53 deletion in vivo blocked Western diet-induced dyslipidemia and hepatic inflammatory transcriptomic activation. Surprisingly, metabolic protection in CD53 KO mice was more pronounced in the presence of an inciting inflammatory event. CD53 deletion attenuated tumor necrosis factor alpha-induced and fatty acid + lipopolysaccharide-induced cytokine gene expression and hepatocyte triglyceride accumulation in isolated murine hepatocytes. In vivo, CD53 deletion in nonalcoholic steatohepatitis diet-fed mice blocked peripheral adipose accumulation and adipose inflammation, insulin tolerance, and liver lipid accumulation. We then defined a stabilized and trehalase-resistant trehalose polymer that blocks hepatocyte CD53 expression in basal and over-fed contexts. The data suggest that CD53 integrates inflammatory and metabolic signals in response to hepatocyte nutritional status and that CD53 blockade may provide a means by which to attenuate pathophysiology in diseases that integrate overnutrition and inflammation, such as nonalcoholic steatohepatitis and type 2 diabetes

Marketing as a means to transformative social conflict resolution: lessons from transitioning war economies and the Colombian coffee marketing system

Social conflicts are ubiquitous to the human condition and occur throughout markets, marketing processes, and marketing systems.When unchecked or unmitigated, social conflict can have devastating consequences for consumers, marketers, and societies, especially when conflict escalates to war. In this article, the authors offer a systemic analysis of the Colombian war economy, with its conflicted shadow and coping markets, to show how a growing network of fair-trade coffee actors has played a key role in transitioning the country’s war economy into a peace economy. They particularly draw attention to the sources of conflict in this market and highlight four transition mechanisms — i.e., empowerment, communication, community building and regulation — through which marketers can contribute to peacemaking and thus produce mutually beneficial outcomes for consumers and society. The article concludes with a discussion of implications for marketing theory, practice, and public policy

Molecular typing and growth curves of serially isolated strains of <i>B. petrii.</i>.

<p>(A) The DiversiLab Non fermentor typing kit was used for rep-PCR typing of <i>B. petrii</i> using DNA from clinical and reference strains. Amplicons were detected with the Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, CA) and data analyzed with the DiversiLab software (version 3.3). Results generated include a dendrogram (left) and virtual gel images (right). (B) Genomic DNA was digested with the restriction endonuclease <i>XbaI</i> and separated by PFGE with a CHEF Mapper system. Asterisks indicate band differences among the patient strains. Ladder: Lambda DNA Ladder 48.5 KB–1 MB kb plugs (Lonza). (C) Growth curves were performed on LB broth at 37°C and growth assessed by colony-forming units (CFU) performed with serially diluted aliquots plated on SBA plates. Graph shows mean and SEM from three experiments. <i>B. petrii</i> 1–5: strains of <i>B. petrii</i> serially isolated from our patient; BAA-461: type strain of <i>B. petrii</i> (ATCC BAA-461); 13363: first described clinical strain of <i>B. petrii</i> (NCTC 13363).</p

Serum susceptibility of <i>B. petrii</i> 1 and <i>B. petrii</i> 3.

<p>Bacterial colonies grown on SBA were resuspended in 1% proteose peptone - phosphate-buffered saline (PP-PBS) to a concentration of 1×10⁷ CFU/ml. A 100-µl aliquot was then combined with an equal volume of 10% normal human serum (NHS) diluted in 1% PP-PBS. A 1% PP-PBS (0% serum) solution and heat-inactivated (56°C for 1 hour) normal human serum (HI-NHS) served as controls. Samples were incubated for 2 hours at 37°C with shaking. After incubation, samples were serially diluted, plated onto sheep blood agar plates, and grown 24–48 h at 37°C to determine the number of CFU and calculate % of survival.</p

Immunoblots with patient’s serum against her own and reference strains.

<p>An aliquot containing 10 µg of protein from the soluble (A) and insoluble (B) fractions obtained from <i>B. petrii</i> strains was electrophoresed on 12% SDS–PAGE, and then transferred to PVDF membrane. The membrane was incubated with the patient serum (1∶5000 dilution) obtained ∼2 months after isolation of <i>B. petrii</i> 3 and then horseradish peroxidase conjugated sheep anti-human IgG (1∶10000). The blots were developed using the enhanced chemiluminescence kit. <i>B. petrii</i> 4, <i>B. petrii</i> 4b, <i>B. petrii</i> 4c and <i>B. petrii</i> 4d refer to four different colonies obtained from the primary isolation plate of <i>B. petrii</i> 4. Fig. 2B had a shorter exposure time than Fig. 2A, so bands could be better visualized. If using similar exposure times, the intensity of the bands in Fig. 2B is 48% higher than in Fig. 2A (as determined by densitometric analysis).</p