Regulation of Adipocyte Differentiation and Metabolism: Rab5-Guanine Nucleotide Exchange Factors and Methylglyoxal
Doctor of Philosophy (PhD)
Dietetics and Nutrition
First Advisor's Name
Fatma G. Huffman
First Advisor's Committee Title
Second Advisor's Name
M. Alejandro Barbieri
Second Advisor's Committee Title
Third Advisor's Name
Third Advisor's Committee Title
Fourth Advisor's Name
Juan P. Liuzzi
Fourth Advisor's Committee Title
Fifth Advisor's Name
Fifth Advisor's Committee Title
Adipocyte, 3T3-L1, Adipogenesis, Methylglyoxal, Rab5-GEF, RAP6, Endocytosis, Obesity, Diabetes, Cardiovascular Disease, Ethnic Minority
Date of Defense
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 of PPARγ, C/EBPα and p-Akt1-Ser473, but appeared to be neutralized by RAP6 overexpression. The findings suggest that RAP6 may be a key modulator in regulating the stimulatory effect of methylglyoxal on preadipocyte differentiation. The associations of predominant methylglyoxal-derived adduct, methylglyoxal hydroimidazolone 1 (MGH1), with selected risk factors of chronic diseases in Black participants with and without type 2 diabetes (n=234 controls and n=254 cases) were also investigated. Only in individuals with diabetes, MGH1 levels were positively associated with fasting plasma glucose (B=0.240, p=0.037), homocysteine (B=0.355, p=0.014) and triglyceride (B=0.190, p=0.049). Being African Americans with type 2 diabetes was associated with lower MGH1 levels as compared to being Haitian American with diabetes (B=-0.334, p=0.016). The findings suggest that methylglyoxal may be linked to hyperglycemia and metabolic changes in type 2 diabetes, and may differently impact the development of diabetes across Black subgroups.
Chantarasinlapin, Praew, "Regulation of Adipocyte Differentiation and Metabolism: Rab5-Guanine Nucleotide Exchange Factors and Methylglyoxal" (2017). FIU Electronic Theses and Dissertations. 3227.
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