Year: 2008
Type: dissertation
Abstract: ABSTRACT \nMetformin is the most common drug used against type 2 diabetes \nmellitus. However, it was only recently shown, in human and rat \nhepatocytes, that metformin-like 5-aminoimidazole-4-carboximide \nribonucleoside (AICAR), acts via activation of the AMP-activated protein \nkinase (AMPK), an enzyme that plays a central role in lipid metabolism. \nAlthough it is well known that metformin is used in the treatment of type \n2 diabetes and results in significant fat loss, no study has investigated \nthe effects of this drug on adipocytes. In this report I studied the effects \nof metformin on the formation of fat deposits in mouse 3T3-L1 preadipocytes, \nas well as its effects on the activation of AMPK in these cells. \nOur results suggested that metformin significantly inhibits the \ntransformation of pre-adipocytes into adipocytes. This is achieved via the \ninhibition of intracellular lipid accumulation during adipogenesis. In \naddition to its inhibition of intracellular lipid accumulation, metformin \ninduced a significant increase in the phosphorylation of AMPK. \nIt has been shown that AMPK activation with AICAR results in the \ninhibition of the nuclear factor-κB (NF-κB) induced gene expression. Since \nNF-κB is the key nuclear factor used by HIV-1 during the initiation of its \ngene transcription, I investigated the possibility of inhibiting HIV-1 \nreplication in U1 cells with metformin and AICAR. I observed that AICAR \nand metformin inhibit HIV-1 replication in U1 cells. This inhibition wasparalleled by the accumulation of NF-κB in the cytoplasm of AICAR and \nmetformin treated cells, and at the same time by a significant decrease in \nthe concentration of this nuclear factor in the nucleus of these cells. \nHowever, I failed to observe any phosphorylation of AMPK by metformin \nand AICAR in U1 cells. \nIn conclusion, metformin inhibits adipogenesis in mouse adipocytes and \nthis inhibition is likely to take place via the activation of AMPK. AICAR and \nmetformin have inhibitory properties against HIV-1 replication. However, \nthis inhibition does not seem to be by the activation of AMPK.
Author: Kabamba B. Alexandre
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W610168708