To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.

Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome-host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-GF conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is produced by diverse bacterial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chain acyl-CoAs. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with Western diet but not control diet. Thus, VB provides a molecular target to understand and potentially manage microbiome-host symbiosis/dysbiosis in diet-dependent obesity.

A high sugar and high‐fat diet Western‐style diet can result in significant dyslipidemia, often leading to non‐alcoholic fatty liver disease (NAFLD), with females particularly affected by this diet irrespective of total caloric intake. Dietary supplementation with beneficial bacteria has been advocated as therapeutic intervention to modulate liver adiposity resulting from a Western‐style diet. Here, we assess the activity of beneficial bacteria on modulating the impact of a Western‐style diet in female mice. Of those tested, we show that a previously uncharacterized beneficial bacterium, namely Lactococcus lactis sp. cremoris significantly protected against Western style diet‐induced hepatic steatosis, elevated cholesterol levels, glucose intolerance, increased body mass index (BMI), and adiposity. Due to these effects, we propose the use of L. lactis sp. cremoris as a therapeutic modality to promote metabolic health in individuals suffering adverse health events resulting from a Western style diet. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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