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Detian Hu from PKU is our first PhD graduate
Detian Hu successfully defended her PhD thesis and becomes the first doctoral graduate from the team. The title of her thesis is “The role of sphingomyelin in regulating UCP1-dependent non-shivering thermogenesis”.
Two new papers reveal thermogenic regulation by lipids and novel adipocyte populations in renal adipose tissue
Together these results uncover a relation between sphingomyelin abundance and fine-tuning of UCP1-mediated non-shivering thermogenesis, and pave the way for studies of Peri Renal Adipose Tissue physiology and mechanisms controlling the plasticity of brown/white adipocyte phenotypes.
The papers have been published in The Journal Of Lipid Research and eLife
Sphingomyelin Is Involved in Regulating UCP1-Mediated Non-Shivering Thermogenesis
Sphingomyelin Is Involved in Regulating UCP1-Mediated Non-Shivering Thermogenesis
Detian Hu, Houyu Zhang, Zhen Liu, Carlos F Ibáñez, Cai Tie, Meng Xie
Journal of Lipid Research (2024) 10.1016/j.jlr.2024.100559
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Perirenal adipose tissue contains a subpopulation of cold-inducible adipocytes derived from brown-to-white conversion
Perirenal adipose tissue contains a subpopulation of cold-inducible adipocytes derived from brown-to-white conversion
Houyu Zhang, Yan Li, Carlos F Ibáñez, Meng Xie
eLife (2024) 10.7554/elife.93151.3
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New paper defines mouse phenotypes for human ACVR1C missense variants that correlate with altered body fat distribution
Genome-wide studies have identified three missense variants in the human gene ACVR1C, encoding the TGF-β superfamily receptor ALK7, that correlate with altered waist-to-hip ratio adjusted for body mass index (WHR/BMI), a measure of body fat distribution.
In our latest paper, to move from correlation to causation and understand the effects of these variants on fat accumulation and adipose tissue function, we introduced each of the variants in the mouse Acvr1c locus and investigated metabolic phenotypes in comparison with a null mutation.
Mice carrying the I195T variant showed resistance to high fat diet (HFD)-induced obesity, increased catecholamine-induced adipose tissue lipolysis and impaired ALK7 signaling, phenocopying the null mutants. Mice with the I482V variant displayed an intermediate phenotype, with partial resistance to HFD-induced obesity, reduction in subcutaneous, but not visceral, fat mass, decreased systemic lipolysis and reduced ALK7 signaling. Surprisingly, mice carrying the N150H variant were metabolically indistinguishable from wild type under HFD, although ALK7 signaling was reduced at low ligand concentrations.
Together, these results validate ALK7 as an attractive drug target in human obesity and suggest a lower threshold for ALK7 function in humans compared to mice.
The paper has been published in Molecular Metabolism
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Human ACVR1C missense variants that correlate with altered body fat distribution produce metabolic alterations of graded severity in knock-in mutant mice
Human ACVR1C missense variants that correlate with altered body fat distribution produce metabolic alterations of graded severity in knock-in mutant mice
Pawanrat Tangseefa , Hong Jin, Houyu Zhang, Meng Xie & Carlos F. Ibáñez
Molecular Metabolism (2024) 10.1016/j.molmet.2024.101890
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Jinyi Chen, MSc
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RhoGDI phosphorylation by PKC promotes its interaction with death receptor p75 NTR to gate axon growth and neuron survival
RhoGDI phosphorylation by PKC promotes its interaction with death receptor p75 NTR to gate axon growth and neuron survival
Ajeena Ramanujan , Zhen Li, Yanchen Ma, Zhi Lin & Carlos F. Ibáñez (2024)
EMBO Reports doi.org/10.1038/s44319-024-00064-2
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New paper reveals how p75NTR interacts with RhoGDI to regulate axon growth and neuron survival
How receptors juggle their interactions with multiple downstream effectors remains poorly understood.
In our latest paper, we report that the outcome of death receptor p75NTR signaling is determined through competition of effectors for interaction with its intracellular domain, in turn dictated by the nature of the ligand. While NGF induces release of RhoGDI through recruitment of RIP2, thus decreasing RhoA activity in favor of NFkB signaling, MAG induces PKC-mediated phosphorylation of the RhoGDI N-terminus, promoting its interaction with the juxtamembrane domain of p75NTR, disengaging RIP2, and enhancing RhoA activity in detriment of NF-kB. This results in stunted neurite outgrowth and apoptosis in cerebellar granule neurons. If presented simultaneously, MAG prevails over NGF. The NMR solution structure of the complex between the RhoGDI N-terminus and p75NTR juxtamembrane domain reveals previously unknown structures of these proteins and clarifies the mechanism of p75NTR activation.
These results show how ligand-directed competition between RIP2 and RhoGDI for p75NTR engagement determine axon growth and neuron survival. Similar principles are likely at work in other receptors engaging multiple effectors and signaling pathways.
The paper has been published in EMBO Reports
Read the full paper HERE