scholarly journals Functional Characterization of Melanocortin-4 Receptor Mutations Associated with Childhood Obesity

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4544-4551 ◽  
Author(s):  
Ya-Xiong Tao ◽  
Deborah L. Segaloff
Keyword(s):  
Childhood Obesity ◽  
Functional Characterization ◽  
Melanocortin 4 Receptor

Functional characterization of a new human melanocortin-4 receptor homozygous mutation (N72K) that is associated with early-onset obesity

2014 ◽  
Vol 41 (12) ◽  
pp. 7967-7972 ◽  
Author(s):  
Patric J. D. Delhanty ◽  
Elise Bouw ◽  
Martin Huisman ◽  
Resie M. L. Vervenne ◽  
Axel P. N. Themmen ◽  
...  
Keyword(s):  
Early Onset ◽  
Functional Characterization ◽  
Homozygous Mutation ◽  
Melanocortin 4 Receptor

scholarly journals Identification and Functional Characterization of Novel Mutations in the Melanocortin-4 Receptor

Obesity Facts ◽  
2010 ◽  
Vol 3 (5) ◽  
pp. 304-311 ◽  
Author(s):  
Sigri Beckers ◽  
Doreen Zegers ◽  
Fenna de Freitas ◽  
Armand V. Peeters ◽  
Stijn L. Verhulst ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Novel Mutations ◽  
Melanocortin 4 Receptor

scholarly journals Functional Characterization of Melanocortin-3 Receptor Variants Identify a Loss-of-Function Mutation Involving an Amino Acid Critical for G Protein-Coupled Receptor Activation

2004 ◽  
Vol 89 (8) ◽  
pp. 3936-3942 ◽  
Author(s):  
Ya-Xiong Tao ◽  
Deborah L. Segaloff
Keyword(s):  
G Protein ◽  
Functional Characterization ◽  
Receptor Activation ◽  
Dominant Negative ◽  
Supporting Evidence ◽  
Loss Of Function ◽  
Melanocortin 4 Receptor ◽  
Dominant Negative Activity ◽  
G Protein Coupled

Although melanocortin-4 receptor mutations are the cause of the most common monogenic form of obesity, the involvement of the melanocortin-3 receptor (MC3R) in the pathogenesis of obesity is unknown. Earlier studies failed to identify any mutations in obese patients except for the identification of two variants (K6T and I81V) that likely represent polymorphisms. However, a potential mutation (I183N) was recently reported from patients having high-fat contents. We report here the functional characterization of these variants. We show that K6T and I81V have ligand binding and signaling properties similar to wild-type (wt) MC3R, indicating that they are indeed polymorphisms. However, the other variant, I183N, completely lacks signaling in response to agonist stimulation, although it binds ligand with normal affinity and with only slightly decreased capacity. Coexpression of the wt and I183N MC3Rs showed that I183N does not exert dominant-negative activity on wt MC3R. These results provide supporting evidence for the hypothesis proposed in the original case report that MC3R mutation might be a genetic factor that confers susceptibility to obesity, likely due to haploinsufficiency. Further mutations at I183 revealed a discrete requirement for I183 in agonist-induced MC3R activation. The corresponding residue is also important for agonist-induced human melanocortin-4 receptor and lutropin receptor activation. In summary, we identify a residue that is critical for activation of G protein-coupled receptors.

scholarly journals Genetic Screening for Melanocortin-4 Receptor Mutations in a Cohort of Italian Obese Patients: Description and Functional Characterization of a Novel Mutation

2004 ◽  
Vol 89 (2) ◽  
pp. 904-908 ◽  
Author(s):  
Ferruccio Santini ◽  
Margherita Maffei ◽  
Giovanni Ceccarini ◽  
Caterina Pelosini ◽  
Giovanna Scartabelli ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Novel Mutation ◽  
Functional Characterization ◽  
Obese Patients ◽  
Melanocortin 4 Receptor

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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