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In both humans and rodent models, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes, and non‐alcoholic fatty liver disease. The glycine cleavage system and its rate‐limiting enzyme, glycine decarboxylase (GLDC), is a major determinant of plasma glycine levels. The goals of this study were to determine if the increased expression of GLDC contributes to the reduced plasma glycine levels seen in disease states, to characterize the hormonal regulation of GLDC gene expression, and to determine if altered GLDC expression has physiological effects that might affect the development of diabetes. The findings presented here show that hepatic GLDC gene expression is elevated in mouse models of obesity and diabetes, as well as by fasting. We demonstrated that GLDC gene expression is strongly regulated by the metabolic hormones glucagon and insulin, and we identified the signaling pathways involved in this regulation. Finally, we found that GLDC expression is linked to glutathione levels, with increased expression associated with elevated levels of glutathione and reduced expression associated with a suppression of glutathione and increased cellular ROS levels. These findings suggest that the hormonal regulation of GLDC contributes not only to the changes in circulating glycine levels seen in metabolic disease, but also affects glutathione production, possibly as a defense against metabolic disease‐associated oxidative stress.
Ruta Jog; Guohua Chen; Jian Wang; Todd Leff. Hormonal regulation of glycine decarboxylase and its relationship to oxidative stress. Physiological Reports 2021, 9, 1 .
AMA StyleRuta Jog, Guohua Chen, Jian Wang, Todd Leff. Hormonal regulation of glycine decarboxylase and its relationship to oxidative stress. Physiological Reports. 2021; 9 (15):1.
Chicago/Turabian StyleRuta Jog; Guohua Chen; Jian Wang; Todd Leff. 2021. "Hormonal regulation of glycine decarboxylase and its relationship to oxidative stress." Physiological Reports 9, no. 15: 1.
Selma Masri; Colin R. Goding; Todd Leff. Paolo Sassone-Corsi (1956–2020). Cell Metabolism 2020, 32, 501 -503.
AMA StyleSelma Masri, Colin R. Goding, Todd Leff. Paolo Sassone-Corsi (1956–2020). Cell Metabolism. 2020; 32 (4):501-503.
Chicago/Turabian StyleSelma Masri; Colin R. Goding; Todd Leff. 2020. "Paolo Sassone-Corsi (1956–2020)." Cell Metabolism 32, no. 4: 501-503.
Selma Masri; Colin R. Goding; Todd Leff. Paolo Sassone-Corsi (1956–2020). Cell 2020, 182, 1363 -1365.
AMA StyleSelma Masri, Colin R. Goding, Todd Leff. Paolo Sassone-Corsi (1956–2020). Cell. 2020; 182 (6):1363-1365.
Chicago/Turabian StyleSelma Masri; Colin R. Goding; Todd Leff. 2020. "Paolo Sassone-Corsi (1956–2020)." Cell 182, no. 6: 1363-1365.
Selma Masri; Colin R. Goding; Todd Leff. Paolo Sassone-Corsi (1956–2020). Molecular Cell 2020, 79, 871 -873.
AMA StyleSelma Masri, Colin R. Goding, Todd Leff. Paolo Sassone-Corsi (1956–2020). Molecular Cell. 2020; 79 (6):871-873.
Chicago/Turabian StyleSelma Masri; Colin R. Goding; Todd Leff. 2020. "Paolo Sassone-Corsi (1956–2020)." Molecular Cell 79, no. 6: 871-873.
Mouse embryonic stem cells (mESCs) are prototypical in vitro models of pluripotent stem cells. They are characterized by a capacity for infinite self-renewal while retaining the ability to differentiate into each of the cell types of the embryo. The maintenance of their pluripotent state relies on a complex regulatory network involving cytokine signaling and transcriptional controls at genetic and epigenetic levels. More recently, it has become evident that mESC pluripotency requires a specific nutritional environment. We now understand that mESC pluripotency is critically dependent on threonine catabolism for provision of one- and two-carbon donors for pluripotency-related chromatin modifications. In this chapter, we provide a comprehensive overview of the cellular processes required for the maintenance of mESC pluripotency, including signaling pathways, transcriptional networks, and epigenetic regulation. In addition, we discuss the latest developments concerning the unique dependence of mESC on threonine and the role of the amino acid in establishing the epigenetic status required for mESC self-renewal.
Ruta Jog; Guohua Chen; Todd Leff; Jian Wang. Threonine Catabolism: An Unexpected Epigenetic Regulator of Mouse Embryonic Stem Cells. Handbook of Nutrition, Diet, and Epigenetics 2019, 1585 -1604.
AMA StyleRuta Jog, Guohua Chen, Todd Leff, Jian Wang. Threonine Catabolism: An Unexpected Epigenetic Regulator of Mouse Embryonic Stem Cells. Handbook of Nutrition, Diet, and Epigenetics. 2019; ():1585-1604.
Chicago/Turabian StyleRuta Jog; Guohua Chen; Todd Leff; Jian Wang. 2019. "Threonine Catabolism: An Unexpected Epigenetic Regulator of Mouse Embryonic Stem Cells." Handbook of Nutrition, Diet, and Epigenetics , no. : 1585-1604.
Although the increased incidence of type 2 diabetes since the 1950s is thought to be primarily due to coincident alterations in lifestyle factors, another potential contributing factor in industrialized countries is exposure of the population to environmental pollutants and industrial chemicals. Exposure levels of many environmental toxicants have risen in the same time-frame as the disease incidence. Of particular interest in this regard is the metal lead. Although overall lead exposure levels have diminished in recent decades, there is an under-recognized but persistent occurrence of lead exposure in poor underserved urban populations. Although the neural developmental pathologies induced by lead exposures have been well documented, very little is known about the effect of lead exposure on the incidence of chronic metabolic diseases such as type 2 diabetes. Although our understanding of the metabolic health effects of lead exposure is incomplete, there are studies in model systems and a small amount of epidemiological data that together suggest a deleterious effect of environmental lead exposure on metabolic health. This article reviews the human, animal and in vitro studies that have examined the effects of lead exposure on the development of diabetes and related metabolic conditions.
Todd Leff; Paul Stemmer; Jannifer Tyrrell; Ruta Jog. Diabetes and Exposure to Environmental Lead (Pb). Toxics 2018, 6, 54 .
AMA StyleTodd Leff, Paul Stemmer, Jannifer Tyrrell, Ruta Jog. Diabetes and Exposure to Environmental Lead (Pb). Toxics. 2018; 6 (3):54.
Chicago/Turabian StyleTodd Leff; Paul Stemmer; Jannifer Tyrrell; Ruta Jog. 2018. "Diabetes and Exposure to Environmental Lead (Pb)." Toxics 6, no. 3: 54.
In the setting of obesity, Pb exposure is prodiabetic, causing fasting hyperglycemia and glucose intolerance in rats. A contributing factor to the metabolic effects of Pb may be the direct stimulation of hepatic gluconeogenic gene expression.
Jannifer B. Tyrrell; Samar Hafida; Paul Stemmer; Angie Adhami; Todd Leff. Lead (Pb) exposure promotes diabetes in obese rodents. Journal of Trace Elements in Medicine and Biology 2017, 39, 221 -226.
AMA StyleJannifer B. Tyrrell, Samar Hafida, Paul Stemmer, Angie Adhami, Todd Leff. Lead (Pb) exposure promotes diabetes in obese rodents. Journal of Trace Elements in Medicine and Biology. 2017; 39 ():221-226.
Chicago/Turabian StyleJannifer B. Tyrrell; Samar Hafida; Paul Stemmer; Angie Adhami; Todd Leff. 2017. "Lead (Pb) exposure promotes diabetes in obese rodents." Journal of Trace Elements in Medicine and Biology 39, no. : 221-226.