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Genomes and Genes | B B LowellSummaryAffiliation: Harvard University Country: USA Publications
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Towards a molecular understanding of adaptive thermogenesisB B Lowell
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 404:652-60. 2000..Here we explore these developments in relation to classical physiological views of adaptive thermogenesis...- Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetesC Y Zhang
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02115, USA
Cell 105:745-55. 2001..These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes... - Energy metabolism in uncoupling protein 3 gene knockout miceA J Vidal-Puig
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 275:16258-66. 2000..The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined... - Uncoupling protein 3 (UCP3) stimulates glucose uptake in muscle cells through a phosphoinositide 3-kinase-dependent mechanismC Huppertz
Diabetes Unit, Department of Medicine, Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 276:12520-9. 2001..Thus, UCP3 stimulates glucose transport and GLUT4 translocation to the cell surface in cardiac and skeletal muscle cells by activating a PI3K dependent pathway... - Role of the beta(3)-adrenergic receptor and/or a putative beta(4)-adrenergic receptor on the expression of uncoupling proteins and peroxisome proliferator-activated receptor-gamma coactivator-1O Boss
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA
Biochem Biophys Res Commun 261:870-6. 1999..This effect is probably indirect, as muscle does not seem to express beta(3)-AR. In addition, our data suggest that BRL 37344 and CGP 12177 act, in part, through an as yet unidentified receptor, possibly a beta(4)-AR... - Mice lacking melanin-concentrating hormone are hypophagic and leanM Shimada
Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
Nature 396:670-4. 1998..Our results show that MCH is a critical regulator of feeding and energy balance which acts downstream of leptin and the melanocortin system, and that deletion of a gene encoding a single orexigenic peptide can result in leanness... - Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1P Puigserver
Dana Farber Cancer Institute, Department of Cell Biology, Boston, MA 02115, USA
Mol Cell 8:971-82. 2001..These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1... - The human uncoupling protein-3 gene. Genomic structure, chromosomal localization, and genetic basis for short and long form transcriptsG Solanes
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 272:25433-6. 1997..Our study shows that UCP3 is also coincident with these quantitative trait loci raising the possibility that abnormalities in UCP3 are responsible for obesity in these models... 
Mice lacking ghrelin receptors resist the development of diet-induced obesityJeffrey M Zigman
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 115:3564-72. 2005..Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity...- Adaptive thermogenesis: turning on the heatB B Lowell
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Curr Biol 8:R517-20. 1998..The discovery of a tissue-specific transcriptional coactivator provides new insights into the regulation of thermogenesis by brown adipocytes... - UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissueA Vidal-Puig
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Biochem Biophys Res Commun 235:79-82. 1997..Since UCP3 is minimally expressed in human heart and other critical organs, it is a promising target for anti-obesity drug development aimed at increasing thermogenesis... - Mice expressing human but not murine beta3-adrenergic receptors under the control of human gene regulatory elementsM Ito
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 47:1464-71. 1998..These "humanized" mice should assist us in the development of drugs that may become effective anti-obesity agents in humans... - Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunctionStefan Krauss
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 112:1831-42. 2003..Therefore, superoxide-mediated activation of UCP2 could play an important role in the pathogenesis of beta cell dysfunction and type 2 diabetes... - Leptin receptor signaling in POMC neurons is required for normal body weight homeostasisNina Balthasar
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue RN, Boston, MA 02215, USA
Neuron 42:983-91. 2004..In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis... - The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activityRoberto Coppari
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Cell Metab 1:63-72. 2005..These data demonstrate that leptin signaling in the ARH is sufficient for mediating leptin's effects on glucose homeostasis and locomotor activity... - Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasisHarveen Dhillon
Department of Medicine, Division of Endocrinology, Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Neuron 49:191-203. 2006..These results reveal a critical role for leptin action on VMH neurons... - Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin actionR C Frederich
Division of Endocrinology, Beth Israel Hospital Research North, Boston, Massachusetts 02215, USA
Nat Med 1:1311-4. 1995.... - Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intoleranceA Zisman
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Nat Med 6:924-8. 2000..These mice showed severe insulin resistance and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport in muscle is essential to the maintenance of normal glucose homeostasis... - The mitochondrial uncoupling-protein homologuesStefan Krauss
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Nat Rev Mol Cell Biol 6:248-61. 2005..The obscure roles of the UCP homologues in normal physiology, together with their emerging role in pathophysiology, provide exciting potential for further investigation... - Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic isletsChen-Yu Zhang
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Cell Metab 3:417-27. 2006..In addition, these agents represent lead compounds that comprise a starting point for the development of therapies aimed at treating beta cell dysfunction... - Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weightRen Zhang
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Endocrinology 149:5654-61. 2008..These results suggest that Socs3 in SF1 neurons negatively regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure... - Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesityLaura E Parton
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Nature 449:228-32. 2007..We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes... - PPARgamma: an essential regulator of adipogenesis and modulator of fat cell functionB B Lowell
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachussetts 02115, USA
Cell 99:239-42. 1999 - Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesityP Valet
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 275:34797-802. 2000..This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass... - Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null miceJiandie Lin
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Cell 119:121-35. 2004..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis... - Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in miceC S Mantzoros
Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts, USA
Diabetes 45:909-14. 1996..Thus, beta3 AR agonists via beta3 ARs suppress leptin levels acutely and simultaneously suppress food intake via a mechanism that operates downstream of leptin and two of its putative central targets... - A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2Stefan Krauss
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 99:118-22. 2002..This study establishes that UCP2, expressed at endogenous levels, mediates proton leak in intact cells... - Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistanceClaudia R Vianna
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Cell Metab 4:453-64. 2006..Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver... - Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2GYORGY BAFFY
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Hepatology 35:753-61. 2002..We conclude that increased expression of UCP2 in the livers of mice with genetically or diet-induced obesity exerts neither protective nor deleterious effects on the severity of fatty liver disease... - Brown adipose tissue, beta 3-adrenergic receptors, and obesityB B Lowell
Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Annu Rev Med 48:307-16. 1997..Whether beta 3-selective agonists will be effective anti-obesity agents in humans is presently under investigation... - Uncoupling protein-3 (UCP3): a mitochondrial carrier in search of a functionB B Lowell
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Int J Obes Relat Metab Disord 23:S43-5. 1999..These efforts should be aided by identification of humans with inactivating mutations and/or the generation of gene knockout mice lacking UCP3... - Frataxin activates mitochondrial energy conversion and oxidative phosphorylationM Ristow
Joslin Diabetes Center, Harvard Medical School, Research Division, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 97:12239-43. 2000..Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation... - Suppression of beta cell energy metabolism and insulin release by PGC-1alphaJ Cliff Yoon
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA
Dev Cell 5:73-83. 2003..These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype... - BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosisNika N Danial
Howard Hughes Medical Institute, Dana Faber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 424:952-6. 2003..This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis... - Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imagingAkira Nakayama
Beth Israel Deaconess Medical Center, Boston, MA, USA
Mol Imaging 2:37-49. 2003..Taken together, BAT perfusion can now be measured noninvasively using NIR fluorescent light, and pharmacological modulators of thermogenesis can be screened at relatively high throughput in living animals... - Adipose tissue mass can be regulated through the vasculatureMaria A Rupnick
Division of Cardiovascular Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 99:10730-5. 2002..We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature... - betaAR signaling required for diet-induced thermogenesis and obesity resistanceEric S Bachman
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
Science 297:843-5. 2002..These findings establish that betaARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity... 
Dual role of proapoptotic BAD in insulin secretion and beta cell survivalNika N Danial
Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Nat Med 14:144-53. 2008..Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion...- Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasisJoel K Elmquist
Department of Medicine and Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115, USA
J Comp Neurol 493:63-71. 2005..Finally, although these studies have been illustrative, they also underscore our relative lack of knowledge and highlight the need for more definitive approaches to unravel the functional significance of these pathways... - Mitochondrial dysfunction and type 2 diabetesBradford B Lowell
Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
Science 307:384-7. 2005..Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction... - Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balanceQingchun Tong
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave, Boston, Massachusetts 02215, USA
Nat Neurosci 11:998-1000. 2008..These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance... - Beta-Adrenergic receptors, diet-induced thermogenesis, and obesityBradford B Lowell
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 278:29385-8. 2003 - Regulation of PPAR gamma gene expression by nutrition and obesity in rodentsA Vidal-Puig
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215, USA
J Clin Invest 97:2553-61. 1996..These findings demonstrate in vivo modulation of PPAR gamma mRNA levels over a fourfold range and provide an additional level of regulation for the control of adipocyte development and function... - Divergence of melanocortin pathways in the control of food intake and energy expenditureNina Balthasar
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
Cell 123:493-505. 2005..Disassociation of food intake and energy expenditure reveals unexpected divergence in melanocortin pathways controlling energy balance... - Gene knockout of Acc2 has little effect on body weight, fat mass, or food intakeDavid P Olson
Division of Endocrinology, Children s Hospital Boston, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:7598-603. 2010..The limited impact of Acc2 deletion on energy balance raises the possibility that selective pharmacological inhibition of Acc2 for the treatment of obesity may be ineffective... - Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemiaQingchun Tong
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
Cell Metab 5:383-93. 2007..Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia... - Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heartE D Abel
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 104:1703-14. 1999..Basal and isoproterenol-stimulated isovolumic contractile performance was preserved. Thus, selective ablation of GLUT4 in the heart initiates a series of events that results in compensated cardiac hypertrophy... - EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responsesMichael Lazarus
Department of Neurology and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Nat Neurosci 10:1131-3. 2007..These observations demonstrate that the EP3R-bearing neurons in the median preoptic nucleus are required for fever responses... - Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibresJiandie Lin
Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 418:797-801. 2002..These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination... - VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itchYang Liu
Dana Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA
Neuron 68:543-56. 2010..Our studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch. Elimination of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch... - Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in miceJennifer W Hill
Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Clin Invest 118:1796-805. 2008.... - Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestionEsther van de Wall
Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 12461, USA
Endocrinology 149:1773-85. 2008.... - Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytesPetra Jost
Department of Internal Medicine I, , , Germany
Am J Physiol Endocrinol Metab 283:E146-53. 2002..Furthermore, it indicates insulin receptor-independent, but PI 3-kinase-dependent, potent negative effects of the novel beta(1)-adrenoceptor state on diverse biological end points of insulin action... - Serotonin reciprocally regulates melanocortin neurons to modulate food intakeLora K Heisler
Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge, CB2 2QQ, United Kingdom
Neuron 51:239-49. 2006.... - Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter regionGemma Solanes
Departament de Bioquimica i Biologia Molecular, Universitat de Barcelona, Avda Diagonal 645, E 08028 Barcelona, Spain
Biochem J 386:505-13. 2005..Such regulation suggests a link between UCP3 gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle... - Free fatty acid-induced beta-cell defects are dependent on uncoupling protein 2 expressionJamie W Joseph
Departments of Medicine and Physiology, University of Toronto, Ontario M5S 1A8, Canada
J Biol Chem 279:51049-56. 2004..We propose that higher free fatty acid oxidation rates prevent accumulation of triglyceride in UCP2(-/-) islets, such accumulation being a phenomenon associated with lipotoxicity... - Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat dietJamie W Joseph
Department of Medicine, University of Toronto, Ontario, Canada
Diabetes 51:3211-9. 2002..These results further establish UCP2 as a component in glucose sensing and suggest a possible new aspect of UCP2 function during the progression of type 2 diabetes...