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Trends in Endocrinology and Metabolism: TEM

Yan Tian, Boqiang Peng, Xianghui Fu
The genetic etiology for obesity-related traits remains elusive. Recent studies link novel ADCY3 variants to obesity and diabetes, and identify an important role of ADCY3-mediated signaling at neuronal primary cilia in the predisposition of obesity. These findings provide new information on obesity etiology and suggest potential anti-obesity therapeutic strategies.
February 14, 2018: Trends in Endocrinology and Metabolism: TEM
Livio Casarini, Daniele Santi, Manuela Simoni, Francesco Potì
It is common opinion that maximal activation of luteinizing hormone (LH)-dependent steroidogenic signal occurs at <1% of human LH/choriogonadotropin (hCG) receptor (LHCGR) occupancy. This effect would be a consequence of an excess of receptors expressed on the surface of theca cells, resulting in a pool of LHCGRs remaining unbound (spare). This concept was borrowed from historical pharmacological studies, when discrepancies between ligand-receptor binding and dose-response curves of cAMP were evaluated by treating mouse or rat Leydig cells with hCG in vitro...
February 8, 2018: Trends in Endocrinology and Metabolism: TEM
Miguel López
Hypothalamic AMP-activated protein kinase (AMPK) is an important modulator of whole-body energy homeostasis, particularly within the ventromedial nucleus, where it regulates energy expenditure, glucose, and lipid metabolism. A recent paper in Cell Reports has demonstrated that AMPK in the paraventricular nucleus of the hypothalamus modulates dietary preference for carbohydrate over fat.
February 5, 2018: Trends in Endocrinology and Metabolism: TEM
Abdul-Rizaq Hamoud, Lauren Weaver, David E Stec, Terry D Hinds
Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood...
February 3, 2018: Trends in Endocrinology and Metabolism: TEM
Alba Gonzalez-Franquesa, Mary-Elizabeth Patti
Merging transcriptomics or metabolomics data remains insufficient for metabolic flux estimation. Ramirez et al. integrate a genome-scale metabolic model with extracellular flux data to predict and validate metabolic differences between white and brown adipose tissue. This method allows both metabolic phenotyping and the identification of potential therapeutic targets for obesity.
February 3, 2018: Trends in Endocrinology and Metabolism: TEM
Johan E Harris, Lisa A Baer, Kristin I Stanford
The intrauterine environment can modulate the course of development and confer an enduring effect on offspring health. The effects of maternal diet to impair offspring metabolic health are well established, but the effects of maternal exercise on offspring metabolic health have been less defined. Because physical exercise is a treatment for obesity and type 2 diabetes (T2D), maternal exercise is an appealing intervention to positively influence the intrauterine environment and improve the metabolic health of offspring...
February 2, 2018: Trends in Endocrinology and Metabolism: TEM
Haisen Li, Vittorio Sartorelli
Intermediates generated in several metabolic processes are used to regulate transcription through covalent histone and DNA modifications. In Cell Reports, Das et al. show that acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury.
January 30, 2018: Trends in Endocrinology and Metabolism: TEM
Kenji Ikeda, Pema Maretich, Shingo Kajimura
Two types of thermogenic fat cells, brown adipocytes and beige adipocytes, play a key role in the regulation of systemic energy homeostasis in mammals. Both brown fat and beige fat possess thermogenic properties in addition to common morphological and biochemical characteristics, including multilocular lipid droplets and cristae-dense mitochondria. Recent studies also identify features that are distinct between the two types of thermogenic fat cells, such as their developmental regulation and function. Of particular interest is the role of beige fat in the regulation of glucose homeostasis via uncoupling protein 1 (UCP1)-independent mechanisms...
January 20, 2018: Trends in Endocrinology and Metabolism: TEM
Decio L Eizirik, Anne Op de Beeck
Enteroviruses are important environmental contributors to islet inflammation (insulitis) in type 1 diabetes mellitus (T1DM). A recent study characterized the proteomic alterations induced by Coxsackievirus type B (CVB) infection of human islets. This provides relevant information to decipher the words of the virus-induced 'dialog' between β cells and the immune system that leads to autoimmunity.
January 8, 2018: Trends in Endocrinology and Metabolism: TEM
Changting Xiao, Priska Stahel, Alicia L Carreiro, Kimberly K Buhman, Gary F Lewis
Dietary lipid absorption and lipoprotein secretion by the gut are important in maintaining whole-body energy homeostasis and have significant implications for health and disease. The processing of dietary lipids, including storage within and subsequent mobilization and transport from enterocyte cytoplasmic lipid droplets or other intestinal lipid storage pools (including the secretary pathway, lamina propria and lymphatics) and secretion of chylomicrons, involves coordinated steps that are subject to various controls...
January 3, 2018: Trends in Endocrinology and Metabolism: TEM
Ailine Stolz, Gilbert Schönfelder, Marlon R Schneider
Although endocrine disruptors represent a serious concern to human health, the underlying molecular mechanisms leading to diseases such as cancer remain poorly understood. Recent work has uncovered the epidermal growth factor receptor (EGFR) as a possible mediator of these adverse health effects, with important implications for the role of endocrine disruptors in human diseases.
December 29, 2017: Trends in Endocrinology and Metabolism: TEM
Julia Loeffler, Georg N Duda, F Andrea Sass, Anke Dienelt
Over the past years, basic findings in cancer research have revealed metabolic symbiosis between different cell types to cope with high energy demands under limited nutrient availability. Although this also applies to regenerating tissues with disrupted physiological nutrient and oxygen supply, the impact of this metabolic cooperation and metabolic reprogramming on cellular development, fate, and function during tissue regeneration has widely been neglected so far. With this review, we aim to provide a schematic overview on metabolic links that have a high potential to drive tissue regeneration...
December 28, 2017: Trends in Endocrinology and Metabolism: TEM
Xavier Palomer, Javier Pizarro-Delgado, Emma Barroso, Manuel Vázquez-Carrera
Increased plasma non-esterified fatty acids (NEFAs) link obesity with insulin resistance and type 2 diabetes mellitus (T2DM). However, in contrast to the saturated FA (SFA) palmitic acid, the monounsaturated FA (MUFA) oleic acid elicits beneficial effects on insulin sensitivity, and the dietary palmitic acid:oleic acid ratio impacts diabetes risk in humans. Here we review recent mechanistic insights into the beneficial effects of oleic acid compared with palmitic acid on insulin resistance and T2DM, including its anti-inflammatory actions, and its capacity to inhibit endoplasmic reticulum (ER) stress, prevent attenuation of the insulin signaling pathway, and improve β cell survival...
December 28, 2017: Trends in Endocrinology and Metabolism: TEM
Jillian L Rourke, Queenie Hu, Robert A Screaton
If left unchecked, prediabetic hyperglycemia can progress to diabetes and often life-threatening attendant secondary complications. Central to the process of glucose homeostasis are pancreatic β cells, which sense elevations in plasma glucose and additional dietary components and respond by releasing the appropriate quantity of insulin, ensuring the arrest of hepatic glucose output and glucose uptake in peripheral tissues. Given that β cell failure is associated with the transition from prediabetes to diabetes, improved β cell function ('compensation') has a central role in preventing type 2 diabetes mellitus (T2DM)...
December 27, 2017: Trends in Endocrinology and Metabolism: TEM
Jan Freark de Boer, Folkert Kuipers, Albert K Groen
A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are a subject of intense investigation and are being unraveled in increasing detail. In addition, insight into the complex interactions between cholesterol and bile acid metabolism has increased considerably in the last couple of years...
December 21, 2017: Trends in Endocrinology and Metabolism: TEM
Luc Rochette, Marianne Zeller, Yves Cottin, Catherine Vergely
In patients with diabetes, the hyperglycemia-driven excess generation of reactive oxygen species (ROS) induces oxidative stress (OS) in a variety of tissues. OS is closely associated with chronic inflammation and has a key role in the pathogenesis of vascular complications. The enzymes that generate ROS and gasotransmitters are redox regulated and are implicated in cellular signaling. As a result of cellular metabolism, cells produce significant amounts of carbon monoxide (CO), mainly from heme degradation catalyzed by heme oxygenases (HOs)...
December 14, 2017: Trends in Endocrinology and Metabolism: TEM
Thomas W Grunt
Cancer-specific perturbations of signaling, metabolism, and epigenetics can be a cause and/or consequence of malignant transformation. Evidence indicates that these regulatory systems interact with each other to form highly flexible and robust cybernetic networks that promote malignant growth and confer treatment resistance. Deciphering these plexuses using holistic approaches known from systems biology can be instructive for the future design of novel anticancer strategies. In this review, I discuss novel findings elucidating the multiple molecular interdependence among cancer-specific signaling, cell metabolism, and epigenetics to provide an insightful understanding of how major cancer machineries interact with each other during cancer development and progression, and how this knowledge may be used for future co-targeting strategies...
December 1, 2017: Trends in Endocrinology and Metabolism: TEM
David R Grattan
A recent paper demonstrates that kisspeptin can stimulate the secretion of both prolactin and luteinizing hormone (LH). This provides novel insight into mechanisms that could account for previous observations of concordant patterns of secretion of the two hormones, such as pulsatile secretion with simultaneous pulses, as well as the preovulatory surges of both prolactin and LH.
December 1, 2017: Trends in Endocrinology and Metabolism: TEM
David W Dodington, Harsh R Desai, Minna Woo
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for transducing signals from a variety of metabolically relevant hormones and cytokines including growth hormone, leptin, erythropoietin, IL4, IL6 and IFNγ. A growing body of evidence suggests that this pathway is dysregulated in the context of obesity and metabolic disease. Recent development of animal models has been instrumental in identifying the role of JAK/STAT signaling in the peripheral metabolic organs including adipose, liver, muscle, pancreas, and the immune system...
November 27, 2017: Trends in Endocrinology and Metabolism: TEM
Anne-Marie Lundsgaard, Andreas Mæchel Fritzen, Bente Kiens
This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondrial fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid (TCA) cycle...
January 2018: Trends in Endocrinology and Metabolism: TEM
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