Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

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Abstract

Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the onset and development of diabetes and acute and chronic coronary artery disease. This review reports available evidence on ceramide structure and generation, and discusses their role in cardiometabolic disease, as well as current translational chances and difficulties for ceramide application in the cardiometabolic clinical settings.

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Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes

Elizabeth Sutton, Courtney M. Peterson, Eric Ravussin … (2018)

Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hour feeding period, with dinner before 3 pm) or a control schedule (12-hour feeding period) for five weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and IF’s effects are not solely due to weight loss. Sutton et al. conduct the first supervised controlled feeding trial to test whether intermittent fasting has benefits in humans in the absence of weight loss. Prediabetic men following a form of intermittent fasting called early time-restricted feeding improved their insulin sensitivity, blood pressure, and oxidative stress levels, without losing weight.

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Ceramide-orchestrated signalling in cancer cells.

Samy A F Morad, Myles C Cabot (2013)

One crucial barrier to progress in the treatment of cancer has been the inability to control the balance between cell proliferation and apoptosis: enter ceramide. Discoveries over the past 15 years have elevated this sphingolipid to the lofty position of a regulator of cell fate. Ceramide, it turns out, is a powerful tumour suppressor, potentiating signalling events that drive apoptosis, autophagic responses and cell cycle arrest. However, defects in ceramide generation and metabolism in cancer cells contribute to tumour cell survival and resistance to chemotherapy. This Review focuses on ceramide signalling and the targeting of specific metabolic junctures to amplify the tumour suppressive activities of ceramide. The potential of ceramide-based therapeutics in the treatment of cancer is also discussed.

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Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study

Kelsey Gabel, Kristin K. Hoddy, Nicole Haggerty … (2018)

BACKGROUND: Time restricted feeding decreases energy intake without calorie counting and may be a viable option for weight loss. However, the effect of this diet on body weight in obese subjects has never been examined. OBJECTIVE: This study investigated the effects of 8-h time restricted feeding on body weight and metabolic disease risk factors in obese adults. DESIGN: Obese subjects (n = 23) participated in an 8-h time restricted feeding intervention (ad libitum feeding between 10:00 to 18:00 h, water fasting between 18:00 to 10:00 h) for 12 weeks. Weight loss and other outcomes were compared to a matched historical control group (n = 23). RESULTS: Body weight and energy intake decreased in the time restricted group (–2.6% ± 0.5; –341 ± 53 kcal/d) relative to controls over 12 weeks (P < 0.05). Systolic blood pressure decreased in the time restricted feeding group (–7 ± 2 mm Hg) versus controls (P < 0.05). Fat mass, lean mass, visceral fat mass, diastolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, fasting insulin, HOMA-IR, and homocysteine were not significantly different from controls after 12 weeks (no group×time interaction). CONCLUSION: These findings suggest that 8-h time restricted feeding produces mild caloric restriction and weight loss, without calorie counting. It may also offer clinical benefits by reducing blood pressure.