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WO2003026576A3 - Induction of brown adipocytes by transcription factor nfe2l2 - Google Patents

Induction of brown adipocytes by transcription factor nfe2l2 Download PDF

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Publication number
WO2003026576A3
WO2003026576A3 PCT/US2002/030266 US0230266W WO03026576A3 WO 2003026576 A3 WO2003026576 A3 WO 2003026576A3 US 0230266 W US0230266 W US 0230266W WO 03026576 A3 WO03026576 A3 WO 03026576A3
Authority
WO
WIPO (PCT)
Prior art keywords
nfe2l2
ucp1
expression
increasing
thermogenesis
Prior art date
Application number
PCT/US2002/030266
Other languages
French (fr)
Other versions
WO2003026576A2 (en
Inventor
Leslie P Kozak
Jong S Rim
Original Assignee
Univ Louisiana State
Leslie P Kozak
Jong S Rim
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Louisiana State, Leslie P Kozak, Jong S Rim filed Critical Univ Louisiana State
Priority to AU2002331898A priority Critical patent/AU2002331898A1/en
Publication of WO2003026576A2 publication Critical patent/WO2003026576A2/en
Publication of WO2003026576A3 publication Critical patent/WO2003026576A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

New methods have been developed to treat obesity or other human disorders by increasing the degree of brown adipose thermogenesis, by both increasing the growth and differentiation of brown adipose tissue and increasing its activity. A new use for the transcription factor NFE2l2 was developed to increase BAT thermogenesis by increasing the expression of Ucp1. For the first time, NFE2l2 was found to interact with the NF-E2 motif and to stimulate the expression of Ucp1 (Figure 9). By modulating the expression of the Nfe2l2 gene or the concentration of NFE2l2 protein, changes in brown adipose tissue thermogenesis can be achieved to treat various weight disorders. Additionally, the direct involvement of CREB binding to CRE2 to regulate Ucp1 expression was demonstrated. Furthermore, transient transfection assays of luciferase reporter constructs and site-directed mutagenesis indicated that CRE2 was involved in transcriptional regulation of the Ucp1 through interaction with a phosphorylated CREB. NFE2l2 can be combined with other known transcription factors, e.g., CREB, PGC1, RXR, RAR, and PPAR gamma, to increase BAT thermogenesis by increasing the expression of Ucp1.
PCT/US2002/030266 2001-09-24 2002-09-24 Induction of brown adipocytes by transcription factor nfe2l2 WO2003026576A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002331898A AU2002331898A1 (en) 2001-09-24 2002-09-24 Induction of brown adipocytes by transcription factor nfe2l2

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32440001P 2001-09-24 2001-09-24
US60/324,400 2001-09-24

Publications (2)

Publication Number Publication Date
WO2003026576A2 WO2003026576A2 (en) 2003-04-03
WO2003026576A3 true WO2003026576A3 (en) 2003-06-26

Family

ID=23263411

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/030266 WO2003026576A2 (en) 2001-09-24 2002-09-24 Induction of brown adipocytes by transcription factor nfe2l2

Country Status (2)

Country Link
AU (1) AU2002331898A1 (en)
WO (1) WO2003026576A2 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7772188B2 (en) 2003-01-28 2010-08-10 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
EP2441474B1 (en) 2003-10-17 2015-08-05 Joslin Diabetes Center, Inc. Methods and compositions for modulating adipocyte function
EP1734963A4 (en) 2004-04-02 2008-06-18 Merck & Co Inc Method of treating men with metabolic and anthropometric disorders
US7825098B2 (en) 2005-04-04 2010-11-02 Joslin Diabetes Center, Inc. Methods and compositions for modulating Necdin function
US20100150885A1 (en) 2005-06-01 2010-06-17 Joslin Diabetes Center, Inc. Methods and compositions for inducing brown adipogenesis
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EA020466B1 (en) 2007-06-04 2014-11-28 Синерджи Фармасьютикалз Инк. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
CA2930674A1 (en) 2008-06-04 2009-12-10 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
JP2011528375A (en) 2008-07-16 2011-11-17 シナジー ファーマシューティカルズ インコーポレイテッド Guanylate cyclase agonists useful for the treatment of gastrointestinal disorders, inflammation, cancer, and other disorders
JP5575137B2 (en) 2008-10-22 2014-08-20 メルク・シャープ・アンド・ドーム・コーポレーション Novel cyclic benzimidazole derivatives useful as antidiabetic agents
US8329914B2 (en) 2008-10-31 2012-12-11 Merck Sharp & Dohme Corp Cyclic benzimidazole derivatives useful as anti-diabetic agents
US9044606B2 (en) 2010-01-22 2015-06-02 Ethicon Endo-Surgery, Inc. Methods and devices for activating brown adipose tissue using electrical energy
US8476227B2 (en) 2010-01-22 2013-07-02 Ethicon Endo-Surgery, Inc. Methods of activating a melanocortin-4 receptor pathway in obese subjects
US8895596B2 (en) 2010-02-25 2014-11-25 Merck Sharp & Dohme Corp Cyclic benzimidazole derivatives useful as anti-diabetic agents
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
WO2012116145A1 (en) 2011-02-25 2012-08-30 Merck Sharp & Dohme Corp. Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents
EP2880028B1 (en) 2012-08-02 2020-09-30 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
BR112015019836A2 (en) 2013-02-22 2017-07-18 Merck Sharp & Dohme compound, pharmaceutical composition, and use of a compound
WO2014139388A1 (en) 2013-03-14 2014-09-18 Merck Sharp & Dohme Corp. Novel indole derivatives useful as anti-diabetic agents
JP2016514670A (en) 2013-03-15 2016-05-23 シナジー ファーマシューティカルズ インコーポレイテッド Guanylate cyclase receptor agonists in combination with other drugs
AU2014235215A1 (en) 2013-03-15 2015-10-01 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
US10011637B2 (en) 2013-06-05 2018-07-03 Synergy Pharmaceuticals, Inc. Ultra-pure agonists of guanylate cyclase C, method of making and using same
WO2015051496A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
US20160235807A1 (en) 2013-10-09 2016-08-18 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines
US10080884B2 (en) 2014-12-29 2018-09-25 Ethicon Llc Methods and devices for activating brown adipose tissue using electrical energy
US10092738B2 (en) 2014-12-29 2018-10-09 Ethicon Llc Methods and devices for inhibiting nerves when activating brown adipose tissue
US11072602B2 (en) 2016-12-06 2021-07-27 Merck Sharp & Dohme Corp. Antidiabetic heterocyclic compounds
EP3558298A4 (en) 2016-12-20 2020-08-05 Merck Sharp & Dohme Corp. Antidiabetic spirochroman compounds

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6166192A (en) * 1997-05-30 2000-12-26 Dana-Farber Cancer Institute PGC-1, a novel brown fat PPARγ coactivator
US6403784B1 (en) * 1999-02-09 2002-06-11 Lexicon Genetics Incorporated Human uncoupling proteins and polynucleotides encoding the same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6166192A (en) * 1997-05-30 2000-12-26 Dana-Farber Cancer Institute PGC-1, a novel brown fat PPARγ coactivator
US6403784B1 (en) * 1999-02-09 2002-06-11 Lexicon Genetics Incorporated Human uncoupling proteins and polynucleotides encoding the same

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHAMPIGNY ET AL.: "Evidence from in vitro differentiating cells that adrenoceptor agonists can increase uncoupling protein mRNA level in adipocytes of adult humans: an RT-PCR study", J. OF LIPID RESEARCH, vol. 37, no. 9, September 1996 (1996-09-01), pages 1907 - 1914, XP002963038 *
KLEIN ET AL.: "Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression", MOLECULAR ENDOCRINOLOGY, vol. 14, no. 6, June 2000 (2000-06-01), pages 764 - 773, XP002963035 *
PALOU ET AL.: "The uncoupling protein, thermogenin", INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELL BIOLOGY, vol. 30, no. 1, January 1998 (1998-01-01), pages 7 - 11, XP002963037 *
RICQUIER ET AL.: "Molecular studies of the uncoupling protein", FASEB JOURNAL, vol. 5, no. 9, 1991, pages 2237 - 2242, XP002963039 *
ROSS ET AL.: "Hibernoma formation in transgenic mice and isolation of a Brown adipocyte cell line expressing the uncoupling protein gene", PROC. NATL. ACAD. SCI. USA, vol. 89, no. 16, August 1992 (1992-08-01), pages 7561 - 7565, XP002963036 *

Also Published As

Publication number Publication date
AU2002331898A1 (en) 2003-04-07
WO2003026576A2 (en) 2003-04-03

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