Have a taste for fat? Yes! A sensor in the mouth promotes preference for fatty foods
The sense of taste informs the organism about the quality of ingested food. It comprises five sub-modalities that perceive sweet, salt, sour, bitter, and umami stimuli. The possibility for an additional taste modality directed to lipid has often been suggested because many animals exhibit a spontaneous attraction for fats, but the existence of an actual sensor remained a matter of debate.
In a paper appearing in the November 1 issue of the Journal of Clinical Investigation, Phillipe Besnard and colleagues identify the first candidate for lipid detection in the oral cavity.
The authors combine genetic, morphological, behavioral and physiological approaches to pinpoint the multifunctional glycoprotein CD36 (also termed fatty acid transporter, FAT) as the sensor for fat. They show that lingual stimulation of CD36 by fatty acids influences behavioral and digestive physiology. CD36 gene inactivation fully abolishes both the spontaneous preference for fat and the changes in gastrointenstinal secretions mediated by oral delivery of lipids. These findings unveil one potential pathway mediating fat taste.
The data suggest that an alteration in the fat perception system might increase obesity risk through feeding dysregulation.
In an accompanying commentary, Nada Abumrad writes that this report provides insight into the basis of our preference for fat and may help us devise better strategies to address the addictive potential of dietary fat.
TITLE: CD36 involvement in orosensory detection of dietary lipids : impact on spontaneous fat preference and digestive secretions
Physiologie de la Nutrition ENSBANA, Dijon, France
Phone: +33 380 396 691; Fax: +33 380 396 691; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=25299
TITLE: CD36 determines our desire for dietary fats
Washington University School of Medicine, St. Louis, MO USA
Phone: 314-747-0348; Fax: 314-444-3432; E-mail: nabumrad@WUSTL.EDU
View the PDF of this article at: https://www.the-jci.org/article.php?id=26955
The reason why antiviral therapy can't annihilate HIV infection, and what to do about it
Antiviral therapy has been used to suppress HIV replication and has dramatically improved the clinical course of disease in affected patients. But the existence of viral reservoirs precludes the complete elimination of HIV from treated patients. In a new study appearing on November 1 in The Journal of Clinical Investigation, Tae-Wook Chun and colleagues from the NIH offer new insight into the eradication of HIV in infected individuals receiving antiviral therapy.
The authors focused on HIV-infected patients who had received effective antiviral therapy for extended periods of time and examined the nature of their residual virus as well as the underlying mechanisms of viral persistence. They demonstrate that HIV persists in both resting and activated CD4+ T cells of patients having received up to 9.1 years of effective antiviral therapy with undetectable levels of HIV in their plasma.
Their data also suggest that latently infected, resting CD4+ T cells may become reactivated, most likely as a result of normal immunologic responses to various antigens and cytokines. In turn, virions released during the reactivation process may spread to neighboring resting as well as activated CD4+ T cells; direct cell-to-cell spread in the absence of virion release may also occur.
The study could impact the design of future therapies aimed at eradicating HIV in patients who have received effective antiviral therapy for extended periods of time. Considering that reactivation of latently infected, resting CD4+ T cells contributes to the persistence of HIV and initiation of new infection cycles, co-administration of an effective and safe reagent that is capable of dampening cellular activation could minimize the spread of virions to uninfected bystander cells.
TITLE: HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir
NIAID/NIH, Bethesda, MD USA
Phone: 301-496-0890; Fax: 301-402-5920; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=26197
Mutating immune system genes leads to more RAGged syndromes than we thought
Certain mutations in the Recombination Activating Genes RAG1 and RAG2 cause a syndrome known as severe combined immunodeficiency, where patients lack immune T and B cells; whereas other mutations in RAG1 and 2 lead to Omenn syndrome (OS), where a few autoimmune T-cell clones responsible for the phenotype expand.
In a new study appearing on November 1 in The Journal of Clinical Investigation, Jean-Pierre de Villartay and colleagues from INSERM report another novel clinical and immunological phenotype associated with recessive RAG1 hypomorphic mutations in 4 patients from 4 different families.
The patients have severe CMV infection and autoimmune blood cell manifestations. This observation extends the range of clinical and immunological phenotypes associated with RAG mutations, emphasizing the role of the genetic background and microbial environment in determining disease phenotype.
An accompanying commentary by Rebecca Buckley states, "the recognition of a new syndrome caused by RAG1 mutations should alert all physicians who care for patients with recurrent infections that atypical presentations may occur when genes of the immune system are mutated."
TITLE: novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection
INSERM, Paris, France
Phone: 331 444 95071; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=25178
TITLE: Variable phenotypic expression of mutations in genes of the immune system
Rebecca H. Buckley
Duke Medical Center, Durham, NC USA
Phone: 919-684-2922; Fax: 919-681-7979; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=26956
New role for nNOS in vascular homeostasis
In a new study appearing on November 1 in The Journal of Clinical Investigation, Michael Ward and colleagues from the University of Toronto demonstrate, for the first time, that the neuronal isoform of nitric oxide synthase (nNOS) is a hypoxia-inducible enzyme in vascular smooth muscle. Investigation of the mechanism by which hypoxia activates nNOS expression revealed the existence of a novel human nNOS promoter, which gives rise to an nNOS mRNA containing a region that permits rapid translation of the full-length protein. Thus, alternate promoters can serve not only to direct transcriptional activation in a developmental stage- and tissue- specific manner but can also confer the ability to rapidly alter cell phenotype in response to a specific survival threat with a functionally significant effect on vascular function.
In an accompanying commentary, Gregg Semenza writes that this paper shows that changes in oxygen concentration can have effects on nNOS enzyme activity and gene expression that contribute to vascular homeostasis under conditions of acute and chronic hypoxia.
TITLE: Hypoxia Induces a Functionally Significant and Translationally Efficient Neuronal Nitric Oxide Synthase mRNA Variant
Michael E. Ward
St. Michael's Hospital, Toronto, ON, CAN
Phone: 416-864-6060 ext 4140; Fax: 416 864 5349; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=20806
TITLE: New insights into nNOS regulation of vascular homeostasis
Gregg L. Semenza
The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Phone: 410-955-1619; Fax: 443-287-5618; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=26792
Being a 7 transmembrane receptor without G protein coupling can break the heart
Receptors that span the cell membrane seven times (7-transmembrane receptors) typically relay signals from outside the cell by coupling to G proteins inside the cell. Rarely, the signal transduction is G protein independent, but the physiological consequences of this unconventional mechanism have not been clear.
In a new study appearing on November 1 in The Journal of Clinical Investigation, Junichi Sadoshima and colleagues from UMDNJ show a clear consequence of G protein independent signaling through the angiotensin type 2 receptor (AT1R) in the heart.
The authors made transgenic mice with cardiac specific overexpression of AT1R with a mutation in the second intracellular loop. These mice had impaired cardiac function compared to mice with normal AT1R.
An accompanying commentary states that these results "not only provide the first glimpse of the physiological effects of this newly appreciated mode of signaling but also provide important and previously unappreciated clues as to the underlying molecular mechanisms."
TITLE: Cardiac-specific overexpression of AT1 receptor mutant lacking G alpha q/G alpha i coupling causes hypertrophy and bradycardia in transgenic Mice
University of Medicine and Dentistry of New Jersey, Newark, NJ USA
Phone: 973-972-8916; Fax: 973-972-8919; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=25330
TITLE: When 7 transmembrane receptors are not G protein–coupled receptors
Howard A. Rockman
Duke University Medical Center, Durham, NC USA
Phone: 919 668 2521; Fax: 919 668 2524; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=26950
B cells and liver fibrosis: what's the link?
Liver fibrosis is a major problem in a variety of human liver pathologies. In a new study appearing on November 1 in The Journal of Clinical Investigation, Tatiana Novobrantseva and colleagues from Biogen use a rodent model of hepatic fibrosis to show, for the first time, that B cell deficient mice have attenuated fibrosis in response to chemically induced hepatic tissue injury.
This work provides evidence that a component of the adaptive immune system is involved in regulating hepatic tissue injury and remodeling. In an accompanying commentary Rashpal Bhogal and Constantin Boda write, "this study provides new insight into our understanding of the cells involved in mediating the adaptive immune response that leads to hepatic fibrosis."
TITLE: Attenuated Liver Fibrosis in the Absence of B Cells
Biogen, Cambridge, MA USA
Phone: 617-914-7178; Fax: 617-679-3148; E-mail: Tatiana.Novobrantseva@biogenidec.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=24798
TITLE: B cells: no longer bystanders in liver fibrosis
Mount Sinai School of Medicine, New York, NY USA
Phone: 212-241-6924; Fax: 212-423-0711; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=26845
A new and surprising way to decrease food intake and body weight
It is important to understand the regulation of energy balance in light of the rising rates of obesity and obesity-related disorders. In a new study appearing on November 1 in The Journal of Clinical Investigation, Jacquelyn Reed and colleagues from the University of Cincinatti describe a novel role for the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) to regulate energy balance via actions in the central nervous system.
The authors show that central administration of rodent, but not human GM-CSF, suppresses food intake and produces significant weight loss. Even when food intake is suppressed, GM-CSF-treated rats have more weight loss, as a result of increased energy expenditure. The same doses that suppress food intake when given centrally have no impact when given peripherally, indicating that the central nervous system is the target organ for GM-CSF actions. Like leptin, GM-CSF suppresses the expression of the orexigenic hypothalamic neuropeptides NPY and AgRP.
The authors also show that circulating levels of GM-CSF are not influenced by feeding and fasting and that expression of GM-CSF in adipose tissue, liver, muscle and lung are not altered by fasting. Mice with targeted disruption of GM-CSF show increased weight gain and body fat.
These findings show that GM-CSF signaling in the central nervous system can regulate energy homeostasis.
TITLE: GM-CSF action in the CNS decreases food intake and body weight
University of Cincinnati, Cincinnati, OH USA
Phone: 513-558-3432; Fax: 513-558-8990; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=25681
Forget what you know about excitoxicity – there's a new player in town
Current evidence suggests that blocking excitatory NMDA-type glutamate receptor channels is sufficient to prevent excitotoxic injury and subsequent neurodegeneration that is the substrate for neurologic disease. But a new study appearing on November 1 in The Journal of Clinical Investigation by Matthew Bellizzi and colleagues from University of Rochester suggests otherwise.
The authors show that synaptic pathology, characterized by beading of dendrites is similar in a variety of neurodegenerative diseases, incluing HIV-1 associated dementia (HAD). They then expose dissociated hippocampal neurons and brain slices to platelet activating factor (PAF). PAF is an inflammatory lipid generated by post-synaptic neurons during excitatory neurotransmission and also from infiltrating macrophages and activated microglia in patients with HIV-1 infection. In HAD patients, PAF is dramatically elevated and can replicate HIV-1 associated dendritic pathology.
Thus, physiological synaptic activity becomes toxic in neurons that are exposed to high levels of PAF, in the absence of excitotoxic glutamate release. The studies suggest a paradigm shift in how neurodegeneration occurs in the central nervous system of patients living with HIV-1 and other neurodegenerative diseases that have a component of inflammation.
TITLE: Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor
University of Rochester School of Medicine, Rochester, NY USA
Phone: 585 275-9954; Fax: 585 276-1966; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=25444
Spastic neurodegenerative disease model flies away
Hereditary Spastic Paraplegias (HSP) are a group of neurodegenerative diseases characterized by progressive weakness and spasticity of the lower limbs. Dominant mutations in the human SPG4 gene, encoding a protein called spastin, are responsible for the most frequent form of HSP. The Drosophila homologue of spastin, Dspastin, has been recently shown to regulate microtubule stability and synaptic function in this fly.
In a new study appearing on November 1 in The Journal of Clinical Investigation, Andrea Daga and colleagues from University of Padova report the generation of a Drosophila HSP model. The authors show that neural knockdown of Dspastin and neural overexpression of Dspastin containing a conserved pathogenic mutation, both recapitulate some phenotypic aspects of the human disease, including adult onset, locomotor impairment and neurodegeneration.
The authors also show that the microtubule targeting drug vinblastine attenuates these phenotypes in vivo. Thus, loss of spastin function elicits HSP-like phenotypes in Drosophila, providing insight into the molecular mechanism of spastin mutations. Therapy with Vinca alkaloids may be useful in spastin-associated HSP and other disorders related to microtubule dysfunction.
In an accompanying commentary, Ellen Penny and Brian McCabe write that these results "confirm the usefulness of Drosophila genetic models to understand HSP and other neurodegenerative diseases."
TITLE: Disease-related phenotypes in a Drosophila model of Hereditary Spastic Paraplegia are ameliorated by treatment with the microtubule destabilizing agent vinblastine
Dulbecco Telethon Institute, University of Padova, Padova, ITALY
Phone: 003 904 9827 5778; E-mail: firstname.lastname@example.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=24694
TITLE: All neuropathies great and small
Columbia University, New York, NY USA
Phone: 212 305-3548; Fax: 212-305-5775; E-mail: email@example.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=27003
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.
What is a cynic? A man who knows the price of everything and the value of nothing.
-- Oscar Wilde