Life Sciences Commons^™

Modulating Adipogenesis: Key Role Of Ras-Related Protein Rab5 And Its Effectors, Yongjun Huang

FIU Electronic Theses and Dissertations

The formation of adipocytes is a complicated process in which insulin and IGF-1 signaling pathways and numerous transcription factors control the conversion of precursor cells to mature fat cells. The Rab5 protein acts as a rate-limiting protein during receptor-mediated endocytosis by switching between a GDP-bound inactive form and a GTP-bound active form. The inactivation and activation of Rab5 are regulated by several Rab5 GTPase activating proteins (GAPs) and Rab5 guanine nucleotide exchange factors (GEFs), respectively.

This dissertation demonstrated that the activity of the small GTPase Rab5 and its regulators are essential for the differentiation of 3T3-L1 pre-adipocytes. Specifically, it showed …

Regulation Of Adipocyte Differentiation And Metabolism: Rab5-Guanine Nucleotide Exchange Factors And Methylglyoxal, Praew Chantarasinlapin

FIU Electronic Theses and Dissertations

Internalization and trafficking of ligand-receptor complex rely on a particular set of proteins, e.g. small GTPase protein Rab5 and its activators called guanine nucleotide exchange factors. Rab5-activating protein 6 (RAP6), a Vps9-containing protein, may participate in Rab5-mediated insulin signaling and receptor trafficking. A dicarbonyl compound methylglyoxal was found to alter insulin signaling in preadipocytes. This dissertation aimed to investigate the association of RAP6 activity on 3T3-L1 preadipocyte differentiation and those driven by methylglyoxal. Overexpression of RAP6 inhibited preadipocyte differentiation, Ser473-phosphorylation of Akt1, and expression of adipogenic marker PPARγ, but not C/EBPα. Methylglyoxal (10 µM) increased preadipocyte differentiation, proliferation and expression …

The Effects Of Artemisia Derived Natural Products On Adipogenesis, Steven Abood

FIU Electronic Theses and Dissertations

For the first time in human history, more people worldwide suffer from obesity than are undernourished. Numerous health complications are associated with obesity including cardiovascular disease, Type 2 Diabetes, cancers of reproductive tissues, stroke, depression, anxiety disorders, and Alzheimer’s disease. A deeper understanding of the anti-adipogenic effects and mechanism of action of sesquiterpene lactones may have pharmacological import in the continuing search for therapeutic modalities to ameliorate the effects of this global obesity epidemic.

Dehydroleucodine (DhL), 11,13-dihydro-dehydroleucodine (DH-DhL), and dehydroparashin-B (DhP), sesquiterpene lactones extracted from or derived from compounds extracted from Artemisia douglasiana, were investigated for their anti-adipogenic effects …

Novel Insights Into The Mechanisms Of Regulation Of Tyrosine Kinase Receptors By Ras Interference 1, Adriana Galvis

FIU Electronic Theses and Dissertations

Receptor-tyrosine kinases (RTKs) are membrane bound receptors characterized by their intrinsic kinase activity. RTK activities play an essential role in several human diseases, including cancer, diabetes and neurodegenerative diseases. RTK activities have been regulated by the expression or silencing of several genes as well as by the utilization of small molecules.

Ras Interference 1 (Rin1) is a multifunctional protein that becomes associated with activated RTKs upon ligand stimulation. Rin1 plays a key role in receptor internalization and in signal transduction via activation of Rab5 and association with active form of Ras. This study has two main objectives: (1) It determines …