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Trends in Endocrinology and Metabolism: TEM

Kei Sakamoto, Laurent Bultot, Olga Göransson
The discovery of liver kinase B1 (LKB1) as an upstream kinase for AMP-activated protein kinase (AMPK) led to the identification of several related kinases that also rely on LKB1 for their catalytic activity. Among these, the salt-inducible kinases (SIKs) have emerged as key regulators of metabolism. Unlike AMPK, SIKs do not respond to nucleotides, but their function is regulated by extracellular signals, such as hormones, through complex LKB1-independent mechanisms. While AMPK acts on multiple targets, including metabolic enzymes, to maintain cellular ATP levels, SIKs primarily regulate gene expression, by acting on transcriptional regulators, such as the cAMP response element-binding protein-regulated transcription coactivators and class IIa histone deacetylases...
October 29, 2018: Trends in Endocrinology and Metabolism: TEM
Rinke Stienstra, Mihai G Netea
In addition to the impact of Bacillus Calmette-Guerin (BCG) vaccination on antimicrobial host defence, a novel study reveals beneficial effects on glycaemic control in patients with long-standing type 1 diabetes mellitus (T1DM). These effects are ascribed to an accelerated glucose consumption in immune cells due to increased glycolysis and reduced oxidative phosphorylation.
October 13, 2018: Trends in Endocrinology and Metabolism: TEM
Jianhua Xiong
Metabolism has recently been in the spotlight because of technical advances in metabolite measurement; however, it is not a new topic in the Nobel Prize's history. Emerging evidence suggests that metabolism is more complex than was previously believed. Retrospective analysis of the Nobel Prize-winning metabolic discoveries may inspire future studies.
October 9, 2018: Trends in Endocrinology and Metabolism: TEM
Francis de Zegher, Abel López-Bermejo, Lourdes Ibáñez
Polycystic ovary syndrome (PCOS) development commonly starts with a mismatch between pre- and postnatal weight gain, leading to hepatovisceral fat excess. To escape from such central obesity, girls may accelerate their growth and/or maturation. This homeostatic mechanism is lost upon reaching adult height, and PCOS may ensue. Prevention and/or treatment of PCOS should aim at reducing central fat excess.
October 5, 2018: Trends in Endocrinology and Metabolism: TEM
Antonio Simone Laganà, Simone Garzon, Jvan Casarin, Massimo Franchi, Fabio Ghezzi
Myo-inositol (MI) and D-chiro-inositol (DCI) are insulin second messengers, and MI is involved in follicular gonadotropin pathways which orchestrate ovulation. The tissue-specific MI/DCI ratio is modulated by insulin through aromatase and is altered in insulin resistance (IR), with reduced epimerization of MI to DCI in insulin-sensitive tissues. In ovaries, the MI/DCI ratio is 100:1, but is dramatically reduced by insulin-stimulated epimerase in hyperinsulinemic women with polycystic ovary syndrome (PCOS). Inositols have proved to be effective in PCOS, improving metabolic and hormonal state, and restoring spontaneous ovulation...
September 27, 2018: Trends in Endocrinology and Metabolism: TEM
Z Hochberg
An evolutionary approach to obesity involves a genomic/anthropological dimension. For 1.8 Myr the lifestyle of hunter-gatherers (HGs) comprised intense physical activity and a high-protein/low-carbohydrate diet. Genomes of HGs were adapted to low insulin sensitivity. When the agrarian epoch began a new 'farmer diet' high in carbohydrates (CHO) emerged. Owing to periodic famines, the genome may not have adapted; they preserved a HG genome. Ever since the industrial revolution our genome is adapting rapidly to a CHO-rich diet...
September 19, 2018: Trends in Endocrinology and Metabolism: TEM
Yuichi Takashi, Seiji Fukumoto
Fibroblast growth factor (FGF) 23 is a bone-derived phosphotropic hormone that regulates phosphate and vitamin D metabolism. FGF23 mainly affects kidney function via the FGF receptor (FGFR)/α-Klotho complex. The physiological roles of FGF23 and α-Klotho in the regulation of mineral homeostasis have been well established. In addition, recent studies have reported that FGF23 has various effects on many other tissues, sometimes in an α-Klotho-independent manner, especially under pathological conditions. However, how FGF23 works in these tissues without α-Klotho is not entirely clear...
September 11, 2018: Trends in Endocrinology and Metabolism: TEM
Kirsty A Walters, Robert B Gilchrist, William L Ledger, Helena J Teede, David J Handelsman, Rebecca E Campbell
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-aged women. It is characterized by reproductive, endocrine, metabolic, and psychological features. The cause of PCOS is unknown, thus there is no cure and its management remains suboptimal because it relies on the ad hoc empirical management of symptoms only. We review here the strong support for PCOS having a neuroendocrine origin. In particular, we focus on the role of aberrant hypothalamic-pituitary function and associated hyperandrogenism, and their role as major drivers of the mechanisms underpinning the development of PCOS...
September 5, 2018: Trends in Endocrinology and Metabolism: TEM
Jingjing Cai, Xiao-Jing Zhang, Hongliang Li
Non-alcoholic fatty liver disease (NAFLD) has become the most epidemic liver disease worldwide owing to rapid changes in lifestyle over the past few decades. This chronic condition intertwines with low-grade inflammation and metabolic disequilibrium, and potentiates the onset and progression of devastating hepatic and extrahepatic complications. In addition to an integral role in promoting host defense, recent studies also implicate innate immune signaling in a multitude of processes that control the progression of NAFLD...
August 18, 2018: Trends in Endocrinology and Metabolism: TEM
Emma C Johns, Fiona C Denison, Jane E Norman, Rebecca M Reynolds
Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. The prevalence is rising and correlates with the increase in maternal obesity over recent decades. The etiology of GDM is complex, with genetic and environmental factors implicated in mechanistic and epidemiological studies. GDM begets important short- and long-term health risks for the mother, developing fetus, and offspring. This includes the high likelihood of subsequent maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes in the offspring...
November 2018: Trends in Endocrinology and Metabolism: TEM
Mariona Graupera, Marc Claret
Metabolic disorders such as obesity are accompanied by endothelial cell (EC) dysfunction and decreased vascular density. The current paradigm posits that metabolic alterations associated with obesity secondarily lead to EC dysfunction. However, in view of recent evidence reporting that EC dysfunction per se is able to cause metabolic dysregulation, this paradigm should be revisited and further elaborated. In this article we summarize current views and discuss evidence in favor of a causal role for ECs in systemic metabolic dysregulation...
November 2018: Trends in Endocrinology and Metabolism: TEM
Amin Ardestani, Kathrin Maedler
Mechanistic target of rapamycin complex (mTORC)1 is the major regulator of metabolism at the cellular and organismal level. mTORC1-mediated regulatory feedback loops enable adaptation to nutrient and growth factor availability and metabolic demand. In their recent study, Yoneyama et al. have identified and characterized a negative feedback loop from mTORC1 to insulin receptor substrate (IRS)1; the key component of the insulin/insulin-like growth factor (IGF) signaling pathway.
November 2018: Trends in Endocrinology and Metabolism: TEM
Xue Jiao, Hanni Ke, Yingying Qin, Zi-Jiang Chen
Premature ovarian insufficiency (POI) is highly heterogeneous in genetic etiology. Yet identifying causative genes has been challenging with candidate gene approaches. Recent approaches using next generation sequencing (NGS), especially whole exome sequencing (WES), in large POI pedigrees have identified new causatives and proposed relevant candidates, mainly enriched in DNA damage repair, homologous recombination, and meiosis. In the near future, NGS or whole genome sequencing will help better define genes involved in intricate regulatory networks...
November 2018: Trends in Endocrinology and Metabolism: TEM
Suowen Xu, Jaroslav Pelisek, Zheng Gen Jin
Atherosclerosis is a chronic inflammatory and lipid-depository disease that eventually leads to acute cardiovascular events. Emerging evidence supports that epigenetic processes such as DNA methylation, histone modification, and noncoding RNAs play an important role in plaque progression and vulnerability, highlighting the therapeutic potential of epigenetic drugs in cardiovascular therapeutics.
November 2018: Trends in Endocrinology and Metabolism: TEM
Raphael Chevre, Carlos Silvestre-Roig, Oliver Soehnlein
Altered nutritional behavior in Western societies has unleashed numerous metabolic disorders, intimately linked to profound disruptions of the immune system. Here we summarize how nutrition modulates innate immunity. We outline recent findings regarding nutrient signaling and we particularly focus on the collateral impact of nutrition on the microbiome and on the bile acid (BA) pool. We discuss how the integration of postprandial signals by the gut microbiota, along with the absorption routes of metabolites, differentially affects immune niches to orchestrate immune responses...
October 2018: Trends in Endocrinology and Metabolism: TEM
Marc N Wein, Marc Foretz, David E Fisher, Ramnik J Xavier, Henry M Kronenberg
Salt-inducible kinases (SIKs) represent a subfamily of AMP-activated protein kinase (AMPK) family kinases. Initially named because SIK1 (the founding member of this kinase family) expression is regulated by dietary salt intake in the adrenal gland, it is now apparent that a major biological role of these kinases is to control gene expression in response to extracellular cues that increase intracellular levels of cAMP. Here, we review four physiologically relevant examples of how cAMP signaling impinges upon SIK cellular function...
October 2018: Trends in Endocrinology and Metabolism: TEM
Jun Ren, James R Sowers, Yingmei Zhang
Recent advances in health care have improved the management of cardiometabolic disorders, and prolonged lifespan. However, the ever-rising prevalence of metabolic stress related to obesity (insulin resistance, diabetes, hypertension, and dyslipidemia) has greatly challenged geriatric care. The ubiquitin-proteasome system and autophagy-lysosomal pathways represent two major, yet distinct cellular machineries, for degradation and removal of damaged or long-lived proteins and organelles; the function of which declines with aging...
October 2018: Trends in Endocrinology and Metabolism: TEM
Anders M Näär
The miR-33 microRNAs (miRNAs) are crucial regulators of cholesterol/lipids, and may represent therapeutic targets for the treatment of atherosclerosis. A recent report by Price et al. showed that miR-33 knockout (KO) mice exhibit obesity, insulin resistance, and increased food intake, suggesting that metabolic regulation by miR-33 is more complex than was previously known.
October 2018: Trends in Endocrinology and Metabolism: TEM
Rajashree Mishra, Kenyaita M Hodge, Diana L Cousminer, Richard D Leslie, Struan F A Grant
Latent autoimmune diabetes in adults (LADA) is characterized by the presence of islet autoantibodies and initial insulin independence, which can lead to misdiagnosis of type 2 diabetes (T2D). As such, understanding the genetic etiology of LADA could aid in more accurate diagnosis. However, there is ongoing debate regarding the exact definition of LADA, so understanding its impact in different populations when contrasted with type 1 diabetes (T1D) and T2D is one potential strategy to gain insight into its etiology...
September 2018: Trends in Endocrinology and Metabolism: TEM
Almudena Veiga-Lopez, Yong Pu, Jeremy Gingrich, Vasantha Padmanabhan
Endocrine disrupting chemicals (EDCs) are compounds that are part of everyday consumer products and industrial manufacturing processes. EDCs can interfere with the endocrine system, including the adipose tissue. Accumulating evidence from epidemiological, animal, and in vitro studies demonstrates that EDCs can alter body weight, adipose tissue expansion, circulating lipid profile, and adipogenesis, with some resulting in transgenerational effects. These outcomes appear to be mediated through multiple mechanisms, from nuclear receptor binding to epigenetic modifications...
September 2018: Trends in Endocrinology and Metabolism: TEM
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