Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been extensively studied for its preferential ability to induce apoptosis of cancer cells. Beyond the cytotoxic capacity of TRAIL, new physiological and pathological roles for TRAIL have been identified, and there is now growing evidence supporting its involvement in the development of obesity and diabetes. This review summarizes the most recent findings associating TRAIL with obesity and diabetes in both humans and experimental settings. We also present and discuss some of the reported controversies behind TRAIL signaling and function. Understanding TRAIL mechanism(s) in vivo and its involvement in disease may lead to novel strategies to combat the growing pandemic of obesity and diabetes worldwide.
Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring.
Paternal high fat diet (HFD) consumption triggers unique gene signatures, consistent with premature aging and chronic degenerative disorders, in both white adipose tissue (RpWAT) and pancreatic islets of daughters. In addition to published data in Nature, 2010, 467, 963-966 (GSE: 19877, islet) and FASEB J 2014, 28, 1830-1841 (GSE: 33551, RpWAT), we describe here additional details on systems-based approaches and analysis to develop our observations. Our data provides a resource for exploring the complex molecular mechanisms that underlie intergenerational transmission of obesity.