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Marin L Gantner, Bethany C Hazen, Elodie Eury, Erin L Brown, Anastasia Kralli
Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial protein UCP1, which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor α (ERRα)...
October 20, 2016: Endocrinology
Yutong Su, Xiuli Jiang, Yanli Li, Feng Li, Yulong Cheng, Ying Peng, Dalong Song, Jie Hong, Guang Ning, Yanan Cao, Weiqing Wang
The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion...
October 18, 2016: Endocrinology
Sandip K Boss, Irina Hutson, Charles Harris
Exogenous glucocorticoid (GC) administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia and hypertension, a constellation of findings known as Cushing's syndrome. These effects are mediated by the glucocorticoid receptor (GR). Since GR activation in liver and adipose has been implicated in metabolic syndrome we wanted to determine the role of GR in these tissues in the development of metabolic syndrome. Since GRKO mice (whole body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue specific (liver or adipose) GRKO mice using cre-lox technology...
October 18, 2016: Endocrinology
Kristen E Syring, Kayla A Boortz, James K Oeser, Alessandro Ustione, Kenneth A Platt, Melanie K Shadoan, Owen P McGuinness, David W Piston, David R Powell, Richard M O'Brien
Polymorphisms in the SLC30A8 gene, which encodes the ZnT8 zinc transporter, are associated with altered susceptibility to type 2 diabetes (T2D) and SLC30A8 haploinsufficiency is protective against the development of T2D in obese humans. SLC30A8 is predominantly expressed in pancreatic islet beta cells but surprisingly multiple knockout mouse studies have shown little effect of Slc30a8 deletion on glucose tolerance or glucose-stimulated insulin secretion (GSIS). Multiple other Slc30a isoforms are expressed at low levels in pancreatic islets...
October 18, 2016: Endocrinology
Anna P Pilbrow, Kathy A Lewis, Marilyn H Perrin, Wendy E Sweet, Christine S Moravec, W H Wilson Tang, Mark O Huising, Richard W Troughton, Vicky A Cameron
Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)1, Ucn2 and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors...
October 18, 2016: Endocrinology
Yuen Ting Lam, Laura Lecce, Joanne T M Tan, Christina A Bursill, David J Handelsman, Martin K C Ng
Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout mouse strain that contains a transcriptionally inactive AR (AR(Δex3)KO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Castrated wildtype (AR(WT)) and AR(Δex3)KO mice were implanted with dihydrotestosterone (DHT) or placebo pellets following hindlimb ischemia (HLI)...
October 18, 2016: Endocrinology
Ari L Mendell, Carolyn E Creighton, Bettina E Kalisch, Neil J MacLusky
Low free testosterone levels in men are associated with age-related cognitive decline and increased risk for neurotoxicity, resulting in disease. The mechanisms underlying these observations remain poorly defined. While rapid, androgen receptor-dependent activation of extracellular signal-regulated kinase (ERK) has been postulated as a neurotrophic and neuroprotective mechanism, actions of testosterone metabolites such as 5α-androstane-3α,17β-diol (3α-diol) may also be involved. We investigated the influence of 3α-diol on the induction of ERK phosphorylation in SH-SY5Y human female neuroblastoma cells and primary cortical neurons from male and female mice...
October 18, 2016: Endocrinology
Igor Arregi, Maria Climent, Dobromir Iliev, Jürgen Strasser, Nadège Gouignard, Jenny K Johansson, Tania Singh, Magdalena Mazur, Henrik Semb, Isabella Artner, Liliana Minichiello, Edgar M Pera
Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here we show that Retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme...
October 14, 2016: Endocrinology
Kazuki Okamoto, Shizu Hirata-Tsuchiya, Chiaki Kitamura, Kazuki Omoteyama, Toshiyuki Sato, Mitsumi Arito, Manae S Kurokawa, Naoya Suematsu, Tomohiro Kato
Nuclear factor-κB (NF-κB) is the most potent pro-inflammatory transactivator, and an inhibitor of NF-κB is a good anti-inflammatory drug. Glucocorticoids (GCs) are the strongest and the most frequently used anti-inflammatory drugs. GCs-bound glucocorticoid receptor (GR) inhibits the transcriptional activity of NF-κB, and thereby suppresses a broad range of inflammatory processes. Concurrently, in whole body out side of inflammation area, GR exerts a lot of hormone action, which results in severe side effects...
October 14, 2016: Endocrinology
Justin Darcy, Samuel McFadden, Yimin Fang, Joshua A Huber, Chi Zhang, Liou Y Sun, Andrzej Bartke
Ames dwarf mice (Prop1(df/df)) are long-lived due to a loss of function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption (VO2) and heat production, as well as a decrease in their respiratory quotient (RQ). Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature (Tco). Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (eWAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion...
October 14, 2016: Endocrinology
S Pauliina Markkula, David Lyons, Chen-Yu Yueh, Christine Riches, Paul Hurst, Barbara Fielding, Lora K Heisler, Mark L Evans
Specialized metabolic-sensors in the hypothalamus regulate blood glucose levels by influencing hepatic glucose output and hypoglycemic counter regulatory responses. Hypothalamic reactive oxygen species (ROS) may act as a metabolic signal mediating responses to changes in glucose, other substrates and hormones. The role of ROS in the brain's control of glucose homeostasis remains unclear. We hypothesized that hydrogen peroxide (H2O2), a relatively stable form of ROS, acts as a sensor of neuronal glucose consumption and availability and that lowering brain H2O2 with the enzyme catalase would lead to systemic responses increasing blood glucose...
October 14, 2016: Endocrinology
Takashi Umehara, Ikko Kawashima, Tomoko Kawai, Yumi Hoshino, Ken-Ichirou Morohashi, Yuichi Shima, Wenxian Zeng, JoAnne S Richards, Masayuki Shimada
Adult Leydig cells are derived from proliferating stem/progenitor Leydig cells in the infant testis and subsequent differentiation to steroidogenic cells in adult mice. Leydig cell proliferation in the infant testis occurs primarily in response to increased levels of LH that induce Leydig cell expression of neuregulin 1, NRG1. Depletion of NRG1 in Nrg1 mutant mice (Nrg1(flox;flox); Cyp19a1Cre mice) dramatically reduces Leydig cell proliferation in the infant testes leading to reduction of testis weight, epididymial weight and serum testosterone in the adult mutant mice...
October 12, 2016: Endocrinology
Subathra Poopalasundaram, David Chambers, Anthony Graham, Pierre-Marc Bouloux
The hypothalamic gonadotrophin releasing hormone (GnRH) neurons are a small group of cells that regulate the reproductive axis. These neurons are specified within the olfactory placode, delaminate from this structure and then migrate to enter the forebrain before populating the hypothalamus. We have employed microarray technology to analyse the transcriptome of the olfactory placode at a number of key time points for GnRH ontogeny using the chick embryo. This resulted in the identification of a large number of genes whose expression levels change significantly over this period...
October 12, 2016: Endocrinology
Riia K Junnila, Silvana Duran-Ortiz, Ozan Suer, Elahu G Sustarsic, Darlene E Berryman, Edward O List, John J Kopchick
Growth hormone (GH) and insulin like growth factor I (IGF-I) are important for a variety of physiological processes including growth, development and aging. Mice with reduced levels of GH and IGF-I have been shown to live longer than wild type controls. Our laboratory has previously found that mice with aGHreceptor gene knockout (GHRKO) from conception exhibit low rates of cancer, resistance to diet-induced diabetes, and extension of lifespan. The GHRKO mouse as well as other mouse lines with reduced GH action display low IGF-I levels, smaller body size, increased adiposity and increased longevity...
October 12, 2016: Endocrinology
Marcio A Torsoni, Beatriz C Borges, Jessica L Cote, Susan J Allen, Erica Mahany, David Garcia-Galiano, Carol F Elias
A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal (HPG) axis is adaptive when energy reserves are diminished, allowing individual survival and energy accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor of the AMP/ATP ratio and ultimately of energy availability. Activation of AMPK suppresses ATP-consuming processes and stimulates ATP-producing pathways. The AMPK α2 catalytic subunit is expressed in multiple hypothalamic nuclei including those associated with reproductive control, i...
October 12, 2016: Endocrinology
Kostja Renko, Carolin S Hoefig, Corinne Dupuy, Lisbeth Harder, Christian Schwiebert, Josef Köhrle, Lutz Schomburg
Iodotyrosine deiodinase (DEHAL1) is a crucial enzyme in iodine homeostasis. Unbound mono- and diiodotyrosines are indispensable byproducts of thyroid hormone biosynthesis. Their iodine needs to be recovered to avoid iodine deficiency, as observed in genetic defects in DEHAL1. Despite its importance, the enzyme is rarely studied. The deiodination process can be monitored by radioactive tracers or via techniques involving mass spectrometry (MS). However, isotope-labeled molecules are expensive, not always commercially available, and their use is legally restricted, while MS requires sophisticated, costly and sensitive instrumentation...
October 12, 2016: Endocrinology
Patience Meo Burt, Liping Xiao, Caroline Dealy, Melanie C Fisher, Marja M Hurley
Humans with X-linked hypophosphatemia (XLH) and Hyp mice, the murine homologue of the disease, develop severe osteoarthropathy and the precise factors that contribute to this joint degeneration remain largely unknown. Fibroblast growth factor 2 (FGF2) is a key regulatory growth factor in osteoarthritis. Although there are multiple FGF2 isoforms the potential involvement of specific FGF2 isoforms in joint degradation has not been investigated. Mice that overexpress the high molecular weight FGF2 isoforms in bone (HMWTg mice) phenocopy Hyp mice and XLH subjects and Hyp mice overexpress the HMWFGF2 isoforms in osteoblasts and osteocytes...
October 12, 2016: Endocrinology
Jennifer Chi Lo, Anne E O'Connor, Zane B Andrews, Camden Lo, Tony Tiganis, Matthew J Watt, Moira K O'Bryan
Fatty liver, or hepatic steatosis, is an alarmingly common pathology in western societies, in large part because if left unheaded it can lead to life-threatening forms of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. As such, it is essential that we attain a greater understanding of the pathways that control energy partitioning in the liver, and ultimately how they are impacted by environmental factors. Herein, we define the essential requirement for a member of the RAB-like clade of small GTPases, RABL2, in fatty acid metabolism including in microtubule-associated mitochondrial movement within the liver...
October 12, 2016: Endocrinology
Yadanar Moe, Chaw Kyi-Tha-Thu, Tomoko Tanaka, Hiroto Ito, Satowa Yahashi, Ken-Ichi Matsuda, Mitsuhiro Kawata, Goro Katsuura, Fumihiro Iwashige, Ichiro Sakata, Atsushi Akune, Akio Inui, Takafumi Sakai, Sonoko Ogawa, Shinji Tsukahara
We found a novel sexually dimorphic area in the dorsal hypothalamus of mice (hereafter the SDA-DH). The SDA-DH was sandwiched between two known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal cell density. The density of neurons in the SDA-DH was increased in male mice by orchidectomy on the day of birth and decreased in female mice by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth...
October 11, 2016: Endocrinology
Katja Czieselsky, Mel Prescott, Robert Porteous, Pauline Campos, Jenny Clarkson, Frederik J Steyn, Rebecca E Campbell, Allan E Herbison
Using a new tail-tip bleeding procedure and a sensitive ELISA, we describe here the patterns of luteinizing hormone (LH) secretion i) throughout the mouse estrous cycle, ii) in ovariectomized mice, iii) in ovariectomized, estradiol-treated mice that model estrogen negative and positive feedback, and iv) in transgenic GNR23 mice that exhibit allele-dependent reductions in GnRH neuron number. Pulsatile LH secretion was evident at all stages of the estrous cycle with LH pulse frequency being approximately one pulse per hour in metestrous, diestrous, and proestrous mice but much less frequent at estrus (<1 pulse/4h)...
October 7, 2016: Endocrinology
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