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Doctor of Philosophy (PhD)
Year Degree Awarded
Month Degree Awarded
Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for the research involving aging and neurodegenerative diseases, like Alzheimer and Parkinson, etc. Compared with the traditional animal models, this nematode possesses many benefits, such as small body size, short lifespan, complete sequenced genome and more than 65% of the genes associated with human diseases. All these characteristics enable this organism to be an ideal living system for obesity and aging studies. Piceatannol is a natural stilbene with many beneficial effects, such as anti-oxidative, anti-inflammatory, anti-atherogenic activities, however, its role on fat accumulation and aging of whole organism is not known. Our results showed that piceatannol (50 and 100 µM) significantly reduced fat accumulation of wild type worms grown in normal and high glucose conditions without altering the growth rate, worm length, pumping rate, or moving speed. The current study further indicated that piceatannol decreased the expression of sbp-1 (encodes an ortholog of mammalian sterol-regulatory-element-binding protein) and its target gene fasn-1 (encodes fatty acid synthase) as well as increased the expression of hosl-1 (encodes an ortholog of hormone-sensitive lipase) in glucose-treated worms. These data suggested that piceatannol reduced fat accumulation in C. elegans by suppression of genes involved in lipid synthesis and possibly through stimulation of lipolysis. Furthermore, piceatannol (50 and 100 µM) significantly extended the lifespan of C. elegans and delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. The current study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires the insulin/IGF-1 signaling (IIS) pathway and sir-2.1 (encodes sirtuin). Research has shown that permethrin, a Type-I pyrethroid, increases triglyceride (fat) accumulation in adipocytes. Little is known, however, about any similar effect of deltamethrin, a Type-II pyrethroid, which produces a distinct syndrome of poisoning in mammals compared with permethrin. Our study indicated that deltamethrin (10 µM) significantly increased the fat accumulation in wild type C. elegans and concomitantly reduced the total progeny number and locomotive activities in a dose-dependent manner. Deltamethrin increased fat accumulation via aak-2 (an ortholog of AMPKα) and nhr-49 (downstream target of aak-2 with function close to peroxisome proliferator-activated receptor-a) mediated mechanisms. The current study may have important implications in understanding effect of bioactive compounds as well as insecticides on the regulation of fat storage and healthy aging in humans.
SHEN, PEIYI, "A LIVING MODEL FOR OBESITY AND AGING RESEARCH: CAENORHABDITIS ELEGANS" (2018). Doctoral Dissertations. 1193.