Listeria monocytogenes is a Gram-positive facultative anaerobe that is the causative agent of the disease listeriosis. The infectious ability of this bacterium is dependent upon resistance to stressors encountered within the gastrointestinal tract, including bile. Previous studies have indicated bile salt hydrolase activity increases under anaerobic conditions, suggesting anaerobic conditions influence stress responses. Therefore, the goal of this study was to determine if reduced oxygen availability increased bile resistance of L. monocytogenes. Four strains representing three serovars were evaluated for changes in viability and proteome expression following exposure to bile in aerobic or anaerobic conditions. Viability for F2365 (serovar 4b), EGD-e (serovar 1/2a), and 10403S (serovar 1/2a) increased following exposure to 10% porcine bile under anaerobic conditions (P < 0.05). However, HCC23 (serovar 4a) exhibited no difference (P > 0.05) in bile resistance between aerobic and anaerobic conditions, indicating that oxygen availability does not influence resistance in this strain. The proteomic analysis indicated F2365 and EGD-e had an increased expression of proteins associated with cell envelope and membrane bioenergetics under anaerobic conditions, including thioredoxin-disulfide reductase and cell division proteins. Interestingly, HCC23 had an increase in several dehydrogenases following exposure to bile under aerobic conditions, suggesting that the NADH:NAD+ is altered and may impact bile resistance. Variations were observed in the expression of the cell shape proteins between strains, which corresponded to morphological differences observed by scanning electron microscopy. These data indicate that oxygen availability influences bile resistance. Further research is needed to decipher how these changes in metabolism impact pathogenicity in vivo and also the impact that this has on susceptibility of a host to listeriosis.

The association between plasma endothelin-1 (ET-1) and obesity has been documented for decades, yet the contribution of ET-1 to risk factors associated with obesity is not fully understood. In 1994, one of first papers to document this association also noted a positive correlation between plasma insulin and ET-1, suggesting a potential contribution of ET-1 to the development of insulin resistance. Both endogenous receptors for ET-1, ET A and ET B are present in all insulin-sensitive tissues including adipose, liver and muscle, and ET-1 actions within these tissues suggest that ET-1 may be playing a role in the pathogenesis of insulin resistance. Further, antagonists for ET-1 receptors are clinically approved making these sites attractive therapeutic targets. This review focuses on known mechanisms through which ET-1 affects plasma lipid profiles and insulin signalling in these metabolically important tissues and also identifies gaps in our understanding of ET-1 in obesity-related pathophysiology.

Current research supports that obesity and insulin resistance are positively correlated with plasma endothelin‐1 (ET‐1) levels; however, the mechanisms leading to this increase in ET‐1 are not fully understood. Similarly, while some physiological effects of ET‐1 have been characterized, the full complexity of this hormone has yet to be described in tissues outside of the vascular system. To date, one of the best treatments available for morbid obesity, cardiovascular disease, and metabolic syndrome is bariatric surgery to quickly reduce body fat and the factors associated with obesity‐related disease. We hypothesize that vertical sleeve gastrectomy (VSG) will reduce plasma ET‐1 levels. This was tested by measuring plasma ET‐1 levels from twelve obese patients before VSG, 6 weeks after, and 6 months after surgery. The results indicate that 6 weeks following VSG, plasma ET‐1 levels increased by 24%; however, after 6 months, there was a 27% decrease compared to baseline. Average weight loss in this cohort was 11.3±2.4 percent body weight after 6 weeks and 21.4±5.7 percent body weight after 6 months. Interestingly, we observed an inverse relationship between baseline plasma ET‐1 and percent body weight loss 3 months (R2=0.45, p<0.05) and 6 months (R2=0.49, p=0.01) post bariatric surgery. Our results indicate that VSG reduces plasma ET‐1 levels, a possible mechanism for improved metabolic risk in these patients. These data also suggest that ET‐1 may inhibit weight loss or serve as a predictor of weight loss following bariatric surgery. Support or Funding Information This work is supported by NHLBI grant R00 HL127178 to JSS. 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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Current research supports that obesity and insulin resistance are positively correlated with plasma endothelin‐1 (ET‐1) levels; however, the mechanisms leading to this increase in ET‐1 are not fully understood. Similarly, while some physiological effects of ET‐1 have been characterized, the full complexity of this hormone has yet to be described in tissues outside of the vascular system. To date, one of the best treatments available for morbid obesity, cardiovascular disease, and metabolic syndrome is bariatric surgery to quickly reduce body fat and the factors associated with obesity‐related disease. We hypothesize that vertical sleeve gastrectomy (VSG) will reduce plasma ET‐1 levels. This was tested by measuring plasma ET‐1 levels from twelve obese patients before VSG, 6 weeks after, and 6 months after surgery. The results indicate that 6 weeks following VSG, plasma ET‐1 levels increased by 24%; however, after 6 months, there was a 27% decrease compared to baseline. Average weight loss in this cohort was 11.3±2.4 percent body weight after 6 weeks and 21.4±5.7 percent body weight after 6 months. Interestingly, we observed an inverse relationship between baseline plasma ET‐1 and percent body weight loss 3 months (R2=0.45, p<0.05) and 6 months (R2=0.49, p=0.01) post bariatric surgery. Our results indicate that VSG reduces plasma ET‐1 levels, a possible mechanism for improved metabolic risk in these patients. These data also suggest that ET‐1 may inhibit weight loss or serve as a predictor of weight loss following bariatric surgery.Support or Funding InformationThis work is supported by NHLBI grant R00 HL127178 to JSS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Elevated endothelin‐1 (ET‐1) is associated with obesity, as well as insulin resistance. We previously reported that rats lacking functional endothelin type B receptors (ETB) demonstrate improved glucose control. In addition, ETB receptor deficient rats have hypertension due to overactivation of the endothelin type A receptor (ETA). In order to determine the effects of ETA receptor activation on insulin sensitivity, we tested the hypothesis that pharmacological blockade of ETB receptors and dual ETA/ETB receptor inhibition would improve glucose control in Sprague Dawley (SD) rats. SD rats were treated with Bosentan (30 mg/kg/day), Atrasentan (10 mg/kg/day), A‐192621 (10 mg/kg/day), or vehicle over a period of two weeks. At day 7, insulin tolerance testing was performed and tissues were collected at day 14 after a 6‐hour fasting period. Treatment with either the dual ETA/ETB antagonist Bosentan, or the ETB antagonist A‐192621, significantly lowered fasting blood glucose as compared to either vehicle or ETA antagonist (Atrasentan) (82.72±4.2*, 75±6.1*, 99.1±2.0, and 94.8±3.2 mg/dl respectively, *p<0.05 vs. vehicle). In addition, both Bosentan and A‐192621 improved insulin tolerance compared to vehicle treated, while Atrasentan had no effect. There were no differences in plasma cholesterol (LDL or HDL) or triglycerides. These data indicate that blockade of ETB receptors improves glucose control and may be an effective treatment for insulin resistance and pre‐diabetes.Support or Funding InformationThis work is supported by NHLBI grant R00 HL127178 to JSS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.