Research Topics
Genomes and Genes
| Jeffrey S FlierSummaryAffiliation: Harvard University Country: USA Publications
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Detail Information
Publications
Hormone resistance in diabetes and obesity: insulin, leptin, and FGF21Jeffrey S Flier
Harvard University, Harvard Medical School, Boston, MA 02115, USA
Yale J Biol Med 85:405-14. 2012..In this presentation, Dr. Flier discusses his and his wife's research on insulin, leptin, and FGF21 in the context of his reflections upon his life's work and his advice for young investigators...
Lasker lauds leptinJeffrey S Flier
Office of the Dean, Harvard Medical School, Boston, MA 02215, USA
Cell Metab 12:317-20. 2010..By uncovering a critical physiologic system, their discovery markedly accelerated our capacity to apply molecular and genetic techniques to understand obesity...- Lasker lauds leptinJeffrey S Flier
Office of the Dean, Harvard Medical School, Boston, MA 02215, USA
Cell 143:9-12. 2010..By uncovering a critical physiologic system, their discovery markedly accelerated our capacity to apply molecular and genetic techniques to understand obesity... - Gut check: testing a role for the intestinal microbiome in human obesityJeffrey S Flier
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Sci Transl Med 1:6ps7. 2009..This model should encourage investigation of the gut microbiome as a contributor to human metabolic disease and permit discovery of targets for the prevention and treatment of these disorders... - 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... - Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivoFfolliott M Fisher
Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Endocrinology 152:2996-3004. 2011..The direct effects we examined are not dependent on PGC-1α. In addition, FGF21 treatment is associated with decreased serum insulin levels that my affect hepatic function... - Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD miceMaria Koulmanda
Departments of Surgery and Medicine, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:16242-7. 2008..Indeed, the functional mass of beta cells expands in AAT-treated diabetic NOD mice... - Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesityErin E Kershaw
Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 54:1023-31. 2005..These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome... 
Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cellsPaul Kievit
Division of Endocrinology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
Cell Metab 4:123-32. 2006..These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism...- TLR4 links innate immunity and fatty acid-induced insulin resistanceHang Shi
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 116:3015-25. 2006.... - Thyroid hormone regulates hepatic expression of fibroblast growth factor 21 in a PPARalpha-dependent mannerAndrew C Adams
Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 285:14078-82. 2010..These findings indicate a novel regulatory pathway whereby T3 positively regulates hepatic FGF21 expression, presenting a novel therapeutic target for diseases such as non-alcoholic fatty liver disease... - PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivoErin E Kershaw
Div of Endocrinology and Metabolism, Dept of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
Am J Physiol Endocrinol Metab 293:E1736-45. 2007..Thus, PPARgamma positively regulates ATGL mRNA and protein expression in mature adipocytes in vitro and in adipose tissue in vivo, suggesting a role for ATGL in mediating PPARgamma's effects on lipid metabolism... - Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistanceHang Shi
Division of Endocrinology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
Diabetes 55:699-707. 2006..Therefore, overexpression of SOCS3 in adipocytes causes local adipocyte insulin resistance, but it is not sufficient to cause systemic insulin resistance... - Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3Jane K Howard
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nat Med 10:734-8. 2004..The level of Socs3 expression is thus a critical determinant of leptin sensitivity and obesity susceptibility in vivo and this molecule is a potential target for therapeutic intervention... - Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic statesMichael K Badman
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
Cell Metab 5:426-37. 2007..These findings identify hepatic FGF21 as a critical regulator of lipid homeostasis and identify a physiological role for this hepatic hormone... - Region-specific leptin resistance within the hypothalamus of diet-induced obese miceHeike Munzberg
Division of Endocrinology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Endocrinology 145:4880-9. 2004..Defects in leptin action in the ARC may play a role in the pathogenesis of leptin-resistant obesity... - Obesity is a fibroblast growth factor 21 (FGF21)-resistant stateFfolliott M Fisher
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Diabetes 59:2781-9. 2010..However, the expected beneficial effects of endogenous FGF21 to increase glucose tolerance and reduce circulating triglycerides are absent in obesity... - Evidence for constitutive neural cell proliferation in the adult murine hypothalamusMaia V Kokoeva
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Comp Neurol 505:209-20. 2007..Thus, we provide evidence that the adult hypothalamus is constitutively neurogenic and that hypothalamic cell proliferation is highly responsive to mitogen action... - Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissueKaren E Inouye
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 56:2242-50. 2007..Importantly, we conclude that CCL2 is not critical for adipose tissue macrophage recruitment. The dominant factor for recruiting macrophages in adipose tissue during obesity therefore remains to be identified... - Neuroscience. Regulating energy balance: the substrate strikes backJeffrey S Flier
Division of Endocrinology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA
Science 312:861-4. 2006 - Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese miceDavid E G McNay
Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes, and Metabolism, Center for Life Sciences, Boston, Massachusetts, USA
J Clin Invest 122:142-52. 2012..This insight has important implications for our understanding of nutritional regulation of energy balance and brain function... - Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosisMichael K Badman
Associate Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Center for Life Sciences, 7th Floor, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Endocrinology 150:4931-40. 2009..Mice lacking FGF21 cannot respond appropriately to a ketogenic diet, resulting in an impaired ability to mobilize and utilize lipids... - Neurogenesis in the hypothalamus of adult mice: potential role in energy balanceMaia V Kokoeva
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
Science 310:679-83. 2005..These findings link the sustained effect of CNTF on energy balance to hypothalamic neurogenesis and suggest that regulated hypothalamic neurogenesis in adult mice may play a previously unappreciated role in physiology and disease... - Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db miceArtur Czupryn
Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
Science 334:1133-7. 2011..These experiments serve as a proof of concept that transplanted neurons can functionally reconstitute complex neuronal circuitry in the mammalian brain... - Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cellsJeffrey M Blumberg
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 281:11205-13. 2006..Further examination of this hypothesis in vivo may shed new light on the biology of adipogenesis... - Leptin regulation of the mesoaccumbens dopamine pathwayStephanie Fulton
Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
Neuron 51:811-22. 2006..These data define a role for leptin in mesoaccumbens DA signaling and indicate that the mesoaccumbens DA pathway, critical to integrating motivated behavior, responds to this adipose-derived signal... - Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanismNabila Aboulaich
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Diabetes 60:757-65. 2011..Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization... - Combined neural inactivation of suppressor of cytokine signaling-3 and protein-tyrosine phosphatase-1B reveals additive, synergistic, and factor-specific roles in the regulation of body energy balanceNadege Briancon
Division of Endocrinology, Diabetes, and Metabolism, Center for Life Sciences, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Diabetes 59:3074-84. 2010.... - What fuels fatJeffrey S Flier
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, USA
Sci Am 297:72-81. 2007 - FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesisFfolliott M Fisher
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Genes Dev 26:271-81. 2012..We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia... - Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotypeGabriella Segal-Lieberman
Research Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 100:10085-90. 2003..These results highlight the importance of MCH in integration of energy homeostasis downstream of leptin and, in particular, the role of MCH in regulation of energy expenditure... - Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrinErin E Kershaw
Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
Diabetes 55:148-57. 2006..These data suggest that murine ATGL but not adiponutrin contributes to net adipocyte lipolysis and that ATGL and adiponutrin are oppositely regulated by insulin both in vitro and in vivo... - Obesity wars: molecular progress confronts an expanding epidemicJeffrey S Flier
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Cell 116:337-50. 2004.... - Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signalingHang Shi
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
J Biol Chem 279:34733-40. 2004..We conclude that SOCS3 plays an important role in mediating insulin resistance and may be an excellent target for therapeutic intervention in insulin resistance and type II diabetes... - Reduced adiposity and high-fat diet-induced adipose inflammation in mice deficient for phosphodiesterase 4BRen Zhang
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
Endocrinology 150:3076-82. 2009.... - Insulin resistance and lipodystrophy in mice lacking ribosomal S6 kinase 2Karim El-Haschimi
Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
Diabetes 52:1340-6. 2003.... - AgRP in energy balance: Will the real AgRP please stand up?Jeffrey S Flier
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Cell Metab 3:83-5. 2006..A recent paper in Cell Metabolism (Wortley et al., 2005) indicates that AgRP itself is important for feeding and weight gain, but only as mice age, and the mechanism may involve dysfunction of the thyroid axis... - Neuroscience. The fat-brain axis enters a new dimensionJoel K Elmquist
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Science 304:63-4. 2004 - The adipocyte as an active participant in energy balance and metabolismMichael K Badman
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Gastroenterology 132:2103-15. 2007..We also describe other important adipose-derived factors in relation to their metabolic effect... - Ciliary neurotrophic factor and leptin induce distinct patterns of immediate early gene expression in the brainJoseph F Kelly
Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
Diabetes 53:911-20. 2004..Our findings support the hypothesis that CNTF and leptin engage distinct CNS sites and CNTF possesses inflammatory properties distinct from leptin... - Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3T3-L1 adipocytesIphigenia Tzameli
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 279:36093-102. 2004..The active species appears to be different from other PPARgamma ligands identified previously. Our findings suggest that a novel biologically relevant PPARgamma ligand is transiently produced in 3T3-L1 cells during adipogenesis... - The gut and energy balance: visceral allies in the obesity warsMichael K Badman
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Finard 202, 330 Brookline Avenue, Boston, MA 02215, USA
Science 307:1909-14. 2005..These discoveries have led to exploration of novel routes for obesity control, some of which involve gut-derived pathways... - Modification of adverse inflammation is required to cure new-onset type 1 diabetic hostsMaria Koulmanda
Department of Surgery, Harvard Medical School, and Islet Transplantation Research Laboratory, Massachusetts General Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:13074-9. 2007..Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DM... - Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in miceHiroaki Masuzaki
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 112:83-90. 2003..The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder... - Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesityDominique D Pierroz
Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Diabetes 51:1337-45. 2002..In conclusion, treatment with a melanocortin agonist is a promising therapeutic approach to DIO and associated insulin resistance... - Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)--a promising drug target for the treatment of metabolic syndromeHiroaki Masuzaki
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA
Curr Drug Targets Immune Endocr Metabol Disord 3:255-62. 2003..Recently reported selective inhibitors of 11beta-HSD1 can ameliorate severe hyperglycemia in the genetically diabetic obese mice. In summary, 11beta-HSD1 is a promising pharmaceutical target for the treatment of the Metabolic Syndrome... - Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalizationHiroshi Shinyama
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Endocrinology 144:1301-14. 2003..Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling... - Adipose tissue as an endocrine organErin E Kershaw
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Clin Endocrinol Metab 89:2548-56. 2004..A better understanding of the endocrine function of adipose tissue will likely lead to more rational therapy for these increasingly prevalent disorders. This review presents an overview of the endocrine functions of adipose tissue...