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Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Strad Pseudokinases Regulate Axogenesis And Lkb1 Stability, Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi-Ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Rielly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes
Strad Pseudokinases Regulate Axogenesis And Lkb1 Stability, Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi-Ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Rielly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes
Faculty Publications - Department of Biological & Molecular Science
No abstract provided.
Brainstem Raphe Pallidus And The Adjacent Area Contain A Novel Action Site In The Melanocortin Circuitry Regulating Energy Balance, Liugen Lei, Yan Gu, Jonathan G. Murphy, Pinxuan Yu, James L. Smart, Malcolm J. Low, Wei Fan
Brainstem Raphe Pallidus And The Adjacent Area Contain A Novel Action Site In The Melanocortin Circuitry Regulating Energy Balance, Liugen Lei, Yan Gu, Jonathan G. Murphy, Pinxuan Yu, James L. Smart, Malcolm J. Low, Wei Fan
Faculty Publications - Department of Biological & Molecular Science
The central melanocortin system plays a critical role in the regulation of energy balance in rodents and humans. The melanocortin signals in both the hypothalamus and brainstem contribute to this regulation. However, how the melanocortin signals of the hypothalamus interact with those intrinsic to the brainstem in the regulation of energy balance is poorly understood. The brainstem raphe pallidus (RPa) and adjacent areas contain melanocortin 4 receptor (MC4-R)-bearing neurons and sympathetic premotor neurons regulating thermogenesis. Here we report that α-melanocyte-stimulating hormone (α-MSH)-immunoreactive (IR) fibers are in close apposition to MC4-R neurons in the RPa. Retrograde tracing studies revealed a unique …
Glucocorticoids Exacerbate Obesity And Insulin Resistance In Neuron-Specific Proopiomelanocortin-Deficient Mice, James L. Smart, Virgine Tolle, Malcolm J. Low
Glucocorticoids Exacerbate Obesity And Insulin Resistance In Neuron-Specific Proopiomelanocortin-Deficient Mice, James L. Smart, Virgine Tolle, Malcolm J. Low
Faculty Publications - Department of Biological & Molecular Science
Null mutations of the proopiomelanocortin gene (Pomc–/–) cause obesity in humans and rodents, but the contributions of central versus pituitary POMC deficiency are not fully established. To elucidate these roles, we introduced a POMC transgene (Tg) that selectively restored peripheral melanocortin and corticosterone secretion in Pomc–/– mice. Rather than improving energy balance, the genetic replacement of pituitary POMC in Pomc–/–Tg+ mice aggravated their metabolic syndrome with increased caloric intake and feed efficiency, reduced oxygen consumption, increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance. Pair-feeding of Pomc–/–Tg+ mice to the daily intake of lean controls normalized their rate of …
Proopiomelanocortin Neurons In Nucleus Tractus Solitarius Are Activated By Visceral Afferents: Regulation By Cholecystokinin And Opioids, Suzanne M. Appleyard, Timothy W. Bailey, Mark W. Doyle, Young-Ho Jin, James L. Smart, Malcolm J. Low, Michael C. Andresen
Proopiomelanocortin Neurons In Nucleus Tractus Solitarius Are Activated By Visceral Afferents: Regulation By Cholecystokinin And Opioids, Suzanne M. Appleyard, Timothy W. Bailey, Mark W. Doyle, Young-Ho Jin, James L. Smart, Malcolm J. Low, Michael C. Andresen
Faculty Publications - Department of Biological & Molecular Science
The nucleustractus solitarius (NTS) receives dense terminations from cranial visceral afferents, including those from the gastrointestinal (GI) system. Although the NTS integrates peripheral satiety signals and relays this signal to central feeding centers, little is known about which NTS neurons are involved or what mechanisms are responsible. Proopiomelanocortin (POMC) neurons are good candidates for GI integration, because disruption of the POMC gene leads to severe obesity and hyperphagia. Here, we used POMC– enhanced green fluorescent protein (EGFP) transgenic mice to identify NTS POMC neurons. Intraperitoneal administration of cholecystokinin (CCK) induced c-fos gene expression in NTS POMC–EGFP neurons, suggesting that they …
Identification Of Neuronal Enhancers Of The Proopiomelanocortin Gene By Transgenic Mouse Analysis And Phylogenetic Footprinting, Flavio S. J. De Souza, Andrea M. Santangelo, Viviana Bumaschny, Marıa Elena Avale, James L. Smart, Malcolm J. Low, Marcelo Rubinstein
Identification Of Neuronal Enhancers Of The Proopiomelanocortin Gene By Transgenic Mouse Analysis And Phylogenetic Footprinting, Flavio S. J. De Souza, Andrea M. Santangelo, Viviana Bumaschny, Marıa Elena Avale, James L. Smart, Malcolm J. Low, Marcelo Rubinstein
Faculty Publications - Department of Biological & Molecular Science
The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss of function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions …
Activation Of Central Melanocortin Pathways By Fenfluramlne, Lora K. Heisler, Michael A. Cowley, Laurence H. Tecott, Wei Fan, Malcolm J. Low, James L. Smart, Marcelo Rubinstein, Jeffrey B. Tatro, Jacob N. Marcus, Henne Holstege, Charlotte E. Lee, Roger D. Cone, Joel K. Elmquist
Activation Of Central Melanocortin Pathways By Fenfluramlne, Lora K. Heisler, Michael A. Cowley, Laurence H. Tecott, Wei Fan, Malcolm J. Low, James L. Smart, Marcelo Rubinstein, Jeffrey B. Tatro, Jacob N. Marcus, Henne Holstege, Charlotte E. Lee, Roger D. Cone, Joel K. Elmquist
Faculty Publications - Department of Biological & Molecular Science
D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs to prevent and treat obesity. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we show that d-FEN-induced anorexia requires activation of central nervous system melanocortin pathways. These results provide a mechanistic explanation of d-FEN's anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to …