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Glucagon Peptide Family and Adipose Tissue: not that Intimate, just Acquaintances.

Perez-Tilve D.

Endocrinology. 2020 Jan 17. pii: bqaa006. doi: 10.1210/endocr/bqaa006. [Epub ahead of print] No abstract available.


Selection and progression of unimolecular agonists at the GIP, GLP-1, and glucagon receptors as drug candidates.

Knerr PJ, Mowery SA, Finan B, Perez-Tilve D, Tschöp MH, DiMarchi RD.

Peptides. 2019 Nov 28:170225. doi: 10.1016/j.peptides.2019.170225. [Epub ahead of print] Review.


Glucagon-like peptide 1 (GLP-1).

Müller TD, Finan B, Bloom SR, D'Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH.

Mol Metab. 2019 Dec;30:72-130. doi: 10.1016/j.molmet.2019.09.010. Epub 2019 Sep 30. Review.


Insulin-like peptide 5 fails to improve metabolism or body weight in obese mice.

Zaykov AN, Gelfanov VM, Perez-Tilve D, Finan B, DiMarchi RD.

Peptides. 2019 Oct;120:170116. doi: 10.1016/j.peptides.2019.170116. Epub 2019 Jul 23.


A Disulfide Scan of Insulin by [3 + 1] Methodology Exhibits Site-Specific Influence on Bioactivity.

Brunel FM, Mayer JP, Gelfanov VM, Zaykov AN, Finan B, Perez-Tilve D, DiMarchi RD.

ACS Chem Biol. 2019 Aug 16;14(8):1829-1835. doi: 10.1021/acschembio.9b00420. Epub 2019 Aug 6.


A Brain-Melanocortin-Vagus Axis Mediates Adipose Tissue Expansion Independently of Energy Intake.

Holland J, Sorrell J, Yates E, Smith K, Arbabi S, Arnold M, Rivir M, Morano R, Chen J, Zhang X, Dimarchi R, Woods SC, Sanchez-Gurmaches J, Wohleb E, Perez-Tilve D.

Cell Rep. 2019 May 21;27(8):2399-2410.e6. doi: 10.1016/j.celrep.2019.04.089.


'Et Tu, Leptin?'

Perez-Tilve D.

Trends Endocrinol Metab. 2019 Apr;30(4):232-233. doi: 10.1016/j.tem.2019.02.001. Epub 2019 Feb 18.


Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism.

Mroz PA, Finan B, Gelfanov V, Yang B, Tschöp MH, DiMarchi RD, Perez-Tilve D.

Mol Metab. 2019 Feb;20:51-62. doi: 10.1016/j.molmet.2018.12.001. Epub 2018 Dec 5.


Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia.

Rivero-Gutierrez B, Haller A, Holland J, Yates E, Khrisna R, Habegger K, Dimarchi R, D'Alessio D, Perez-Tilve D.

Mol Metab. 2018 Nov;17:28-38. doi: 10.1016/j.molmet.2018.07.012. Epub 2018 Aug 20.


Hepatic Glucagon Receptor Signaling Enhances Insulin-Stimulated Glucose Disposal in Rodents.

Kim T, Holleman CL, Nason S, Arble DM, Ottaway N, Chabenne J, Loyd C, Kim JA, Sandoval D, Drucker DJ, DiMarchi R, Perez-Tilve D, Habegger KM.

Diabetes. 2018 Nov;67(11):2157-2166. doi: 10.2337/db18-0068. Epub 2018 Aug 27.


Glucagon Receptor Signaling Regulates Energy Metabolism via Hepatic Farnesoid X Receptor and Fibroblast Growth Factor 21.

Kim T, Nason S, Holleman C, Pepin M, Wilson L, Berryhill TF, Wende AR, Steele C, Young ME, Barnes S, Drucker DJ, Finan B, DiMarchi R, Perez-Tilve D, Tschöp M, Habegger KM.

Diabetes. 2018 Sep;67(9):1773-1782. doi: 10.2337/db17-1502. Epub 2018 Jun 20.


An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPARγ Ubiquitination.

Peng J, Li Y, Wang X, Deng S, Holland J, Yates E, Chen J, Gu H, Essandoh K, Mu X, Wang B, McNamara RK, Peng T, Jegga AG, Liu T, Nakamura T, Huang K, Perez-Tilve D, Fan GC.

Cell Rep. 2018 Jun 19;23(12):3607-3620. doi: 10.1016/j.celrep.2018.05.065.


Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity.

Agrawal A, Parlee S, Perez-Tilve D, Li P, Pan J, Mroz PA, Kruse Hansen AM, Andersen B, Finan B, Kharitonenkov A, DiMarchi RD.

Mol Metab. 2018 Jul;13:45-55. doi: 10.1016/j.molmet.2018.05.003. Epub 2018 May 11.


Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

Mahbod P, Smith EP, Fitzgerald ME, Morano RL, Packard BA, Ghosal S, Scheimann JR, Perez-Tilve D, Herman JP, Tong J.

Endocrinology. 2018 Jan 1;159(1):388-399. doi: 10.1210/en.2017-00540.


Optimization of peptide-based polyagonists for treatment of diabetes and obesity.

Knerr PJ, Finan B, Gelfanov V, Perez-Tilve D, Tschöp MH, DiMarchi RD.

Bioorg Med Chem. 2018 Jun 1;26(10):2873-2881. doi: 10.1016/j.bmc.2017.10.047. Epub 2017 Nov 2. Review. No abstract available.


Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

Ryan KK, Packard AEB, Larson KR, Stout J, Fourman SM, Thompson AMK, Ludwick K, Habegger KM, Stemmer K, Itoh N, Perez-Tilve D, Tschöp MH, Seeley RJ, Ulrich-Lai YM.

Endocrinology. 2018 Jan 1;159(1):400-413. doi: 10.1210/en.2017-00486.


Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

Quarta C, Clemmensen C, Zhu Z, Yang B, Joseph SS, Lutter D, Yi CX, Graf E, García-Cáceres C, Legutko B, Fischer K, Brommage R, Zizzari P, Franklin BS, Krueger M, Koch M, Vettorazzi S, Li P, Hofmann SM, Bakhti M, Bastidas-Ponce A, Lickert H, Strom TM, Gailus-Durner V, Bechmann I, Perez-Tilve D, Tuckermann J, Hrabě de Angelis M, Sandoval D, Cota D, Latz E, Seeley RJ, Müller TD, DiMarchi RD, Finan B, Tschöp MH.

Cell Metab. 2017 Oct 3;26(4):620-632.e6. doi: 10.1016/j.cmet.2017.08.023. Epub 2017 Sep 21.


Novel Hypothalamic Mechanisms in the Pathophysiological Control of Body Weight and Metabolism.

Perez-Tilve D.

Endocrinology. 2017 May 1;158(5):1085-1094. doi: 10.1210/en.2016-1944. Review.


Native Design of Soluble, Aggregation-Resistant Bioactive Peptides: Chemical Evolution of Human Glucagon.

Mroz PA, Perez-Tilve D, Liu F, Mayer JP, DiMarchi RD.

ACS Chem Biol. 2016 Dec 16;11(12):3412-3420. Epub 2016 Nov 8.


Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease.

Finan B, Clemmensen C, Zhu Z, Stemmer K, Gauthier K, Müller L, De Angelis M, Moreth K, Neff F, Perez-Tilve D, Fischer K, Lutter D, Sánchez-Garrido MA, Liu P, Tuckermann J, Malehmir M, Healy ME, Weber A, Heikenwalder M, Jastroch M, Kleinert M, Jall S, Brandt S, Flamant F, Schramm KW, Biebermann H, Döring Y, Weber C, Habegger KM, Keuper M, Gelfanov V, Liu F, Köhrle J, Rozman J, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Hofmann SM, Yang B, Tschöp MH, DiMarchi R, Müller TD.

Cell. 2016 Oct 20;167(3):843-857.e14. doi: 10.1016/j.cell.2016.09.014. Epub 2016 Oct 6.


Fibroblast activation protein (FAP) as a novel metabolic target.

Sánchez-Garrido MA, Habegger KM, Clemmensen C, Holleman C, Müller TD, Perez-Tilve D, Li P, Agrawal AS, Finan B, Drucker DJ, Tschöp MH, DiMarchi RD, Kharitonenkov A.

Mol Metab. 2016 Jul 16;5(10):1015-1024. doi: 10.1016/j.molmet.2016.07.003. eCollection 2016 Oct.


Pyridyl-alanine as a Hydrophilic, Aromatic Element in Peptide Structural Optimization.

Mroz PA, Perez-Tilve D, Liu F, Gelfanov V, DiMarchi RD, Mayer JP.

J Med Chem. 2016 Sep 8;59(17):8061-7. doi: 10.1021/acs.jmedchem.6b00840. Epub 2016 Aug 25.


Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding.

Loyd C, Magrisso IJ, Haas M, Balusu S, Krishna R, Itoh N, Sandoval DA, Perez-Tilve D, Obici S, Habegger KM.

J Appl Physiol (1985). 2016 Sep 1;121(3):687-98. doi: 10.1152/japplphysiol.00456.2016. Epub 2016 Jul 21.


Unimolecular Polypharmacy for Treatment of Diabetes and Obesity.

Tschöp MH, Finan B, Clemmensen C, Gelfanov V, Perez-Tilve D, Müller TD, DiMarchi RD.

Cell Metab. 2016 Jul 12;24(1):51-62. doi: 10.1016/j.cmet.2016.06.021. Review.


Reappraisal of GIP Pharmacology for Metabolic Diseases.

Finan B, Müller TD, Clemmensen C, Perez-Tilve D, DiMarchi RD, Tschöp MH.

Trends Mol Med. 2016 May;22(5):359-376. doi: 10.1016/j.molmed.2016.03.005. Epub 2016 Mar 30. Review.


Hypothalamic leptin action is mediated by histone deacetylase 5.

Kabra DG, Pfuhlmann K, García-Cáceres C, Schriever SC, Casquero García V, Kebede AF, Fuente-Martin E, Trivedi C, Heppner K, Uhlenhaut NH, Legutko B, Kabra UD, Gao Y, Yi CX, Quarta C, Clemmensen C, Finan B, Müller TD, Meyer CW, Paez-Pereda M, Stemmer K, Woods SC, Perez-Tilve D, Schneider R, Olson EN, Tschöp MH, Pfluger PT.

Nat Commun. 2016 Feb 29;7:10782. doi: 10.1038/ncomms10782.


Incretin-like effects of small molecule trace amine-associated receptor 1 agonists.

Raab S, Wang H, Uhles S, Cole N, Alvarez-Sanchez R, Künnecke B, Ullmer C, Matile H, Bedoucha M, Norcross RD, Ottaway-Parker N, Perez-Tilve D, Conde Knape K, Tschöp MH, Hoener MC, Sewing S.

Mol Metab. 2015 Nov 1;5(1):47-56. doi: 10.1016/j.molmet.2015.09.015. eCollection 2016 Jan.


Calcineurin Links Mitochondrial Elongation with Energy Metabolism.

Pfluger PT, Kabra DG, Aichler M, Schriever SC, Pfuhlmann K, García VC, Lehti M, Weber J, Kutschke M, Rozman J, Elrod JW, Hevener AL, Feuchtinger A, Hrabě de Angelis M, Walch A, Rollmann SM, Aronow BJ, Müller TD, Perez-Tilve D, Jastroch M, De Luca M, Molkentin JD, Tschöp MH.

Cell Metab. 2015 Nov 3;22(5):838-50. doi: 10.1016/j.cmet.2015.08.022. Epub 2015 Sep 24.


Contribution of brown adipose tissue activity to the control of energy balance by GLP-1 receptor signalling in mice.

Heppner KM, Marks S, Holland J, Ottaway N, Smiley D, Dimarchi R, Perez-Tilve D.

Diabetologia. 2015 Sep;58(9):2124-32. doi: 10.1007/s00125-015-3651-3. Epub 2015 Jun 7.



Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH.

Mol Metab. 2015 Mar 21;4(6):437-60. doi: 10.1016/j.molmet.2015.03.005. eCollection 2015 Jun. Review.


Diet-induced obese mice retain endogenous leptin action.

Ottaway N, Mahbod P, Rivero B, Norman LA, Gertler A, D'Alessio DA, Perez-Tilve D.

Cell Metab. 2015 Jun 2;21(6):877-82. doi: 10.1016/j.cmet.2015.04.015. Epub 2015 May 14.


GLP-1 based therapeutics: simultaneously combating T2DM and obesity.

Heppner KM, Perez-Tilve D.

Front Neurosci. 2015 Mar 20;9:92. doi: 10.3389/fnins.2015.00092. eCollection 2015. Review.


Tachykinin-1 in the central nervous system regulates adiposity in rodents.

Trivedi C, Shan X, Tung YC, Kabra D, Holland J, Amburgy S, Heppner K, Kirchner H, Yeo GS, Perez-Tilve D.

Endocrinology. 2015 May;156(5):1714-23. doi: 10.1210/en.2014-1781. Epub 2015 Mar 9.


The melanocortin-4 receptor integrates circadian light cues and metabolism.

Arble DM, Holland J, Ottaway N, Sorrell J, Pressler JW, Morano R, Woods SC, Seeley RJ, Herman JP, Sandoval DA, Perez-Tilve D.

Endocrinology. 2015 May;156(5):1685-91. doi: 10.1210/en.2014-1937. Epub 2015 Mar 2.


A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.

Finan B, Yang B, Ottaway N, Smiley DL, Ma T, Clemmensen C, Chabenne J, Zhang L, Habegger KM, Fischer K, Campbell JE, Sandoval D, Seeley RJ, Bleicher K, Uhles S, Riboulet W, Funk J, Hertel C, Belli S, Sebokova E, Conde-Knape K, Konkar A, Drucker DJ, Gelfanov V, Pfluger PT, Müller TD, Perez-Tilve D, DiMarchi RD, Tschöp MH.

Nat Med. 2015 Jan;21(1):27-36. doi: 10.1038/nm.3761. Epub 2014 Dec 8.


The role of β cell glucagon-like peptide-1 signaling in glucose regulation and response to diabetes drugs.

Smith EP, An Z, Wagner C, Lewis AG, Cohen EB, Li B, Mahbod P, Sandoval D, Perez-Tilve D, Tamarina N, Philipson LH, Stoffers DA, Seeley RJ, D'Alessio DA.

Cell Metab. 2014 Jun 3;19(6):1050-7. doi: 10.1016/j.cmet.2014.04.005. Epub 2014 May 15.


Peptide lipidation stabilizes structure to enhance biological function.

Ward BP, Ottaway NL, Perez-Tilve D, Ma D, Gelfanov VM, Tschöp MH, Dimarchi RD.

Mol Metab. 2013 Sep 5;2(4):468-79. doi: 10.1016/j.molmet.2013.08.008. eCollection 2013.


GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.

Habegger KM, Heppner KM, Amburgy SE, Ottaway N, Holland J, Raver C, Bartley E, Müller TD, Pfluger PT, Berger J, Toure M, Benoit SC, Dimarchi RD, Perez-Tilve D, D'Alessio DA, Seeley RJ, Tschöp MH.

Diabetes. 2014 Feb;63(2):505-13. doi: 10.2337/db13-0511. Epub 2013 Nov 1.


Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans.

Finan B, Ma T, Ottaway N, Müller TD, Habegger KM, Heppner KM, Kirchner H, Holland J, Hembree J, Raver C, Lockie SH, Smiley DL, Gelfanov V, Yang B, Hofmann S, Bruemmer D, Drucker DJ, Pfluger PT, Perez-Tilve D, Gidda J, Vignati L, Zhang L, Hauptman JB, Lau M, Brecheisen M, Uhles S, Riboulet W, Hainaut E, Sebokova E, Conde-Knape K, Konkar A, DiMarchi RD, Tschöp MH.

Sci Transl Med. 2013 Oct 30;5(209):209ra151. doi: 10.1126/scitranslmed.3007218.


Hormones and diet, but not body weight, control hypothalamic microglial activity.

Gao Y, Ottaway N, Schriever SC, Legutko B, García-Cáceres C, de la Fuente E, Mergen C, Bour S, Thaler JP, Seeley RJ, Filosa J, Stern JE, Perez-Tilve D, Schwartz MW, Tschöp MH, Yi CX.

Glia. 2014 Jan;62(1):17-25. doi: 10.1002/glia.22580. Epub 2013 Oct 28.


Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia.

Habegger KM, Al-Massadi O, Heppner KM, Myronovych A, Holland J, Berger J, Yi CX, Gao Y, Lehti M, Ottaway N, Amburgy S, Raver C, Müller TD, Pfluger PT, Kohli R, Perez-Tilve D, Seeley RJ, Tschöp MH.

Gut. 2014 Aug;63(8):1238-46. doi: 10.1136/gutjnl-2013-304583. Epub 2013 Oct 9.


Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via central nervous system ghrelin receptors.

Heppner KM, Piechowski CL, Müller A, Ottaway N, Sisley S, Smiley DL, Habegger KM, Pfluger PT, Dimarchi R, Biebermann H, Tschöp MH, Sandoval DA, Perez-Tilve D.

Diabetes. 2014 Jan;63(1):122-31. doi: 10.2337/db13-0414. Epub 2013 Sep 23.


Brown adipose tissue thermogenesis in the resistance to and reversal of obesity: A potential new mechanism contributing to the metabolic benefits of proglucagon-derived peptides.

Lockie SH, Stefanidis A, Oldfield BJ, Perez-Tilve D.

Adipocyte. 2013 Oct 1;2(4):196-200. doi: 10.4161/adip.25417. Epub 2013 Jun 17. Review.


MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched diet.

Gadang V, Kohli R, Myronovych A, Hui DY, Perez-Tilve D, Jaeschke A.

Am J Physiol Endocrinol Metab. 2013 Aug 15;305(4):E549-56. doi: 10.1152/ajpendo.00197.2013. Epub 2013 Jul 16.


GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats.

Habegger KM, Kirchner H, Yi CX, Heppner KM, Sweeney D, Ottaway N, Holland J, Amburgy S, Raver C, Krishna R, Müller TD, Perez-Tilve D, Pfluger PT, Obici S, DiMarchi RD, D'Alessio DA, Seeley RJ, Tschöp MH.

Diabetes. 2013 Sep;62(9):3261-7. doi: 10.2337/db13-0117. Epub 2013 Jun 17.


The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms.

Müller TD, Müller A, Yi CX, Habegger KM, Meyer CW, Gaylinn BD, Finan B, Heppner K, Trivedi C, Bielohuby M, Abplanalp W, Meyer F, Piechowski CL, Pratzka J, Stemmer K, Holland J, Hembree J, Bhardwaj N, Raver C, Ottaway N, Krishna R, Sah R, Sallee FR, Woods SC, Perez-Tilve D, Bidlingmaier M, Thorner MO, Krude H, Smiley D, DiMarchi R, Hofmann S, Pfluger PT, Kleinau G, Biebermann H, Tschöp MH.

Nat Commun. 2013;4:1968. doi: 10.1038/ncomms2968.


Role of adipose and hepatic atypical protein kinase C lambda (PKCλ) in the development of obesity and glucose intolerance.

Habegger KM, Matzke D, Ottaway N, Hembree J, Holland J, Raver C, Mansfeld J, Müller TD, Perez-Tilve D, Pfluger PT, Lee SJ, Diaz-Meco M, Moscat J, Leitges M, Tschöp MH, Hofmann SM.

Adipocyte. 2012 Oct 1;1(4):203-214.


Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency.

Wilson-Pérez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, Stoffers D, Drucker DJ, Pérez-Tilve D, Seeley RJ.

Diabetes. 2013 Jul;62(7):2380-5. doi: 10.2337/db12-1498. Epub 2013 Feb 22.


Fibroblast growth factor 21 mediates specific glucagon actions.

Habegger KM, Stemmer K, Cheng C, Müller TD, Heppner KM, Ottaway N, Holland J, Hembree JL, Smiley D, Gelfanov V, Krishna R, Arafat AM, Konkar A, Belli S, Kapps M, Woods SC, Hofmann SM, D'Alessio D, Pfluger PT, Perez-Tilve D, Seeley RJ, Konishi M, Itoh N, Kharitonenkov A, Spranger J, DiMarchi RD, Tschöp MH.

Diabetes. 2013 May;62(5):1453-63. doi: 10.2337/db12-1116. Epub 2013 Jan 10.


p62 links β-adrenergic input to mitochondrial function and thermogenesis.

Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, Tschöp MH.

J Clin Invest. 2013 Jan;123(1):469-78. doi: 10.1172/JCI64209. Epub 2012 Dec 21.

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