Searchable abstracts of presentations at key conferences in endocrinology

ea0014oc10.4 | Obesity & metabolism | ECE2007

Restoration of signalling capabilities in total loss of function MC4R mutations

Brumm Harald , Bolze Florian , Friedel Susann , Hinney Anke , Klingenspor Martin , Hebebrand Johannes , Grüters Annette , Biebermann Heike

Objectives: The melanocortin 4 receptor (MC4R) belonging to the large superfamily of G-protein coupled receptors plays a crucial role in hypothalamic weight regulation. In approximately 3–5% of investigated obese patients inactivating MC4R mutations are the underlying molecular cause for early onset obesity. Functional characterisation revealed for specific partial loss of function MC4R mutations that restoration of receptor function is possible by usage of highly potent ...

ea0041oc12.1 | Obesity | ECE2016

Functional characterization of naturally occurring mutations in the melanocortin receptor accesory protein 2 (MRAP2)

Biebermann Heike , Schonnop Laura , Herrfurth Nikolas , Volckmar Anna-Lena , Muller Anne , Peters Triinu , Herpertz Stephan , Antel Jochen , Hebebrand Johannes , Kleinau Gunnar , Hinney Anke

Introduction: The melanocortin 4 receptor (MC4R) is the most important hypothalamic expressed G protein coupled receptor in weight regulation. Mutations in the MC4R are the most frequent genetic cause of obesity. Recently an accessory protein of the MC4R (melanocortin receptor accessory protein 2, MRAP2) was discovered that was found to play a role in body weight regulation. MRAP2 deficient mice develop early-onset obesity. The mechanisms of disturbed weight regulation is pote...

ea0020p472 | Obesity and Metabolism | ECE2009

Melanocortin-4-receptor gene variants: hotspot or identical by descent?

Grothe Jessica , Brumm Harald , Scherag Andre , Friedel Susann , Hinney Anke , Hebebrand Johannes , Illig Thomas , Grallert Harald , Wiegand Susanna , Krude Heiko , Farooqi Sadaf , Gruters Annette , Biebermann Heike

The melanocortin-4-receptor (MC4R) plays an important role in body weight regulation. Mutations in the MC4R gene are the most common genetic cause for obesity. The most frequent Northern European mutation is Y35X, associated with D37V on the same allele. Furthermore, there are two variants with a relatively high frequency: V103I and S127L. In rare cases, we identified the variants V103I and S127L on the same allele. The occurrence of two variants on the same allele makes a fou...

ea0016p538 | Obesity | ECE2008

Molecular insights in dysfunctions of the human melanocortin-4-receptor (MC4R) caused by mutations in the third transmembrane domain (TM3) and the second intracellular loop

Tarnow Patrick , Rediger Anne , Widhalm Kurt , Friedel Susann , Kleinau Gunnar , Bolz Hanno , Bettecken Thomas , Hinney Anke , Krause Gerd , Gruters Annette , Biebermann Heike

Mutations in the hypothalamic expressed MC4R gene are the most frequent cause of monogenetic obesity. This Gαs-Protein coupled receptor (GPCR) is activated by endogenous ligands α- and β-MSH and is inhibited by the only known endogenous inverse agonist and antagonist Agouti related peptide (AgRP). Naturally occurring mutations help to understand activation mechanisms of the human MC4R.We previously described a constitutively act...

ea0016p556 | Obesity | ECE2008

Screening for mutations in the glucose-dependent insulinotrophic polypeptide receptor gene (GIPR) in obese patients with disturbed glucose tolerance

Behm Maria , Ambrugger Petra , Sauber Jeannine , Hinney Anke , Hebebrand Johannes , Friedel Susann , Bronner Gunter , Wiegand Susanna , Krude Heiko , Gruters Annette , Biebermann Heike

Objective: The increasing incidence of obesity is a major health problem world-wide. So far, mutations were identified in genes encoding major contributors in energy homeostasis. With the exception of mutations in the melanocortin-4-receptor gene (MC4R) obesity-causing mutations are very rare. To date great efforts were undertaken to identify gene variants that contribute to polygenic obesity. The GIPR belongs to the large superfamily of G-protein coupled recepto...