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Trends in Endocrinology and Metabolism: TEM

Buffy S Ellsworth, Caitlin E Stallings
Pituitary somatotropes secrete growth hormone (GH), which is essential for normal growth and metabolism. Somatotrope defects result in GH deficiency (GHD), leading to short stature in childhood and increased cardiovascular morbidity and mortality in adulthood. Current hormone replacement therapies fail to recapitulate normal pulsatile GH secretion. Stem cell therapies could overcome this problem but are dependent on a thorough understanding of somatotrope differentiation. Although several transcription factors, signaling pathways, and hormones that regulate this process have been identified, the mechanisms of action are not well understood...
May 11, 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.
May 9, 2018: Trends in Endocrinology and Metabolism: TEM
Laura Légat, Ilse Smolders, Alain G Dupont
No abstract text is available yet for this article.
May 5, 2018: Trends in Endocrinology and Metabolism: TEM
Amin Ardestani, Blaz Lupse, Kathrin Maedler
The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer...
May 5, 2018: Trends in Endocrinology and Metabolism: TEM
Ilpo Huhtaniemi, Outi Hovatta, Antonio La Marca, Gabriel Livera, Danielle Monniaux, Luca Persani, Abdelkader Heddar, Katarzyna Jarzabek, Triin Laisk-Podar, Andres Salumets, Juha S Tapanainen, Reiner A Veitia, Jenny A Visser, Peter Wieacker, Slawomir Wolczynski, Micheline Misrahi
Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation...
April 26, 2018: Trends in Endocrinology and Metabolism: TEM
San-Pin Wu, Rong Li, Francesco J DeMayo
Progesterone acts through the progesterone receptor to direct physiological adaption of the uterus in preparation and completion of pregnancy. Genome-wide transcriptome and cistrome analyses have uncovered new members and novel modifiers of the progesterone signaling pathway. Genetically engineered mice allow functional assessment of newly identified genes in vivo and provide insights on the impact of progesterone receptor-dependent molecular mechanisms on pregnancy at the organ system level. Progesterone receptor isoforms collectively mediate progesterone signaling via their distinct and common downstream target genes, which makes the stoichiometry of isoforms relevant in modifying the progesterone activity...
April 25, 2018: Trends in Endocrinology and Metabolism: TEM
Christopher J Halbrook, Zeribe C Nwosu, Costas A Lyssiotis
Metabolic processes within cells are dynamically interconnected. If mitochondria become defective, cells must rewire their metabolism to survive. Here we highlight recent work by Gaude et al. that used a tunable model of mitochondrial dysfunction combined with metabolic tracing and in silico analyses to define these compensatory pathways.
April 22, 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.
April 21, 2018: Trends in Endocrinology and Metabolism: TEM
Bhagirath Chaurasia, William L Holland, Scott A Summers
Chaurasia and colleagues discuss the provocative new finding that some enzymes in the de novo sphingolipid synthesis pathway have dual roles as transcriptional regulators.
April 20, 2018: Trends in Endocrinology and Metabolism: TEM
Biao Li, Jingjing Fan, Ning Chen
MiR-143 is an miRNA with the function of specifically inhibiting the insulin-AKT pathway via the downregulation of oxysterol-binding protein-related protein 8 (ORP8), thus resulting in the inhibition of AKT phosphorylation, insulin tolerance, and final development of type II diabetes mellitus (T2DM). Aerobic exercise can prevent T2DM by downregulating miR-143. However, the underlying mechanisms for exercise-induced change of miR-143 remain unclear. In the present study, we will summarize the involvement of miR-143 in regulating the development of T2DM and the underlying mechanisms for potential diagnosis, prevention, and treatments, including exercise intervention for T2DM by targeting miR-143...
April 18, 2018: Trends in Endocrinology and Metabolism: TEM
Melissa M Page, James D Johnson
Insulin plays roles in lipid uptake, lipolysis, and lipogenesis, in addition to controlling blood glucose levels. Excessive circulating insulin is associated with adipose tissue expansion and obesity, yet a causal role for hyperinsulinemia in the development of mammalian obesity has proven controversial, with many researchers suggesting it as a consequence of insulin resistance. Recently, evidence that specifically reducing hyperinsulinemia can prevent and reverse obesity in animal models has been presented...
April 14, 2018: Trends in Endocrinology and Metabolism: TEM
Wieneke Dijk, Cédric Le May, Bertrand Cariou
Elevated plasma triglyceride (TG) levels are an independent risk factor for cardiovascular disease (CVD). Proprotein convertase subtilisin-kexin 9 (PCSK9) - a protein therapeutically targeted to lower plasma cholesterol levels - might regulate plasma TG-rich lipoprotein (TRL) levels. We provide a timely and critical review of the current evidence for a role of PCSK9 in TRL metabolism by assessing the impact of PCSK9 gene variants, by reviewing recent clinical data with PCSK9 inhibitors, and by describing the potential mechanisms by which PCSK9 might regulate TRL metabolism...
April 14, 2018: Trends in Endocrinology and Metabolism: TEM
Dorit Samocha-Bonet, Sophie Debs, Jerry R Greenfield
Prediabetes affects approximately 40% of American adults. Randomized trials report that a proportion of individuals with prediabetes develop diabetes despite caloric restriction, physical activity, and/or when treated with metformin, the first-line medication for patients with type 2 diabetes mellitus (T2DM). Currently, there are no valid predictors of the effectiveness of these measures in determining who will and who will not progress to the T2DM state. Few studies have examined the clinical and phenotypic predictors of better and worse glycemic response to lifestyle interventions and metformin in prediabetes and diabetes...
April 14, 2018: Trends in Endocrinology and Metabolism: TEM
Robert D S Pitceathly, Jan-Willem Taanman
Groundbreaking work by Kadenbach and colleagues in the 1980s revealed the presence of 13 subunits in the mammalian mitochondrial cytochrome-c oxidase (COX; Complex IV). This observation stood the test of time until 2012 when it was demonstrated that NDUFA4, a polypeptide previously attributed to mitochondrial Complex I, was a 14th subunit of COX. In his recent opinion article, Kadenbach argued that NDUFA4 is not a subunit of COX. However, based on the findings that NDUFA4 deficiency results in a severe loss of COX activity and that NDUFA4 represents a stoichiometric component of the individual COX complex, we reason that NDUFA4 is a bona fide COX subunit and propose renaming it as COX subunit FA4 (COXFA4)...
April 7, 2018: Trends in Endocrinology and Metabolism: TEM
Shih-Chi Su, Russel J Reiter, Hui-Yi Hsiao, Wen-Hung Chung, Shun-Fa Yang
Melatonin was discovered in the pineal gland and first came to be known as a biochemical synchronizer of circadian rhythm. The molecular mechanisms underlying the broad-spectrum actions of melatonin are not restricted to its interaction with proteins but it also has functional effects after influencing RNA species that have no protein-coding potential. In this review we discuss the current understanding of the melatonin-mediated modulation of noncoding RNA (ncRNA) pathways under different physiological and pathological conditions...
April 6, 2018: Trends in Endocrinology and Metabolism: TEM
Carmen Berasain, Matías A Ávila
The pleiotropic liver kinase B1 (LKB1) controls metabolism, cell polarity, and proliferation in an apparently cell- and context-specific manner. A recent study in Cell Reports has demonstrated that LKB1 is essential to maintain the characteristic quiescence of the liver and to secure genomic integrity during liver regeneration independently of AMPK.
April 5, 2018: Trends in Endocrinology and Metabolism: TEM
Yahya Sohrabi, Rinesh Godfrey, Hannes M Findeisen
Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes.
April 4, 2018: Trends in Endocrinology and Metabolism: TEM
Nina Weisshaar, Alaa Madi, Guoliang Cui
T cells rapidly engage glycolysis upon activation. The signaling pathways through which T cell receptor (TCR) activation initiates glycolysis have been a mystery. A long-awaited answer has been provided by Menk et al., who show that pyruvate dehydrogenase kinase 1 (PDHK1) is in the center of signaling events linking TCR activation to glycolysis.
March 31, 2018: Trends in Endocrinology and Metabolism: TEM
Jason C Kovacic
Endothelial to mesenchymal transition (EndMT) involves cellular phenotypic switching from an endothelial to mesenchymal state. Interest in EndMT has been increasing with the appreciation that it has an important role in several cardiovascular diseases. New evidence indicates that fatty acid oxidation (FAO) and cell metabolism are major factors controlling this process.
March 31, 2018: Trends in Endocrinology and Metabolism: TEM
Peter Mirtschink, Triantafyllos Chavakis
Notch signaling contributes to maintenance of adult tissue homeostasis and is also involved in disease. A recent study demonstrates that inhibition of Dll4-Notch signaling by anti-Dll4 improves pancreatic islet function and insulin production by multiple complementary mechanisms. Thus, anti-Dll4 represents a therapeutic approach for compromised insulin production in diabetes.
March 29, 2018: Trends in Endocrinology and Metabolism: TEM
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