Investigation of the preadipocyte primary cilia signalosome - consequences associated with obesity can be miogated by shioing adipose ossue expansion from hypertrophic to hyperplasoc expansion; the…

Investigation of the preadipocyte primary cilia signalosome - consequences associated with obesity can be miogated by shioing adipose ossue expansion from hypertrophic to hyperplasoc expansion; the former increases overall size of exisong adipocytes and correlates with increased inammaoon, insulin insensiovity, and brosis, while the laer dierenoates new adipocytes from resident preadipocytes through adipogenesis. Remedying the expansion of our adipose ossue to favor healthier hyperplasoc expansion is of the upmost importance to combat the obesity epidemic, as western diets high in FAT and carbohydrates have shown to shio the balance of FAT expansion to the more consequenoal hypertrophic expansion. All preadipocytes have primary cilia, which are criocal for their dierenoaoon into mature adipocytes. These organelles are typically rich in signaling components, specically g protein-coupled receptors (gpcrs), though lile is known about ciliary protein composioon in preadipocytes. Thus far only one receptor has been discovered in the cilium of preadipocytes, and its acovaoon increases ciliary camp and subsequent adipogenesis. Increases in cellular camp are necessary for EX vivo adipogenesis, but IT is unknown what role compartmentalized ciliary camp has in adipogenesis, though ciliary camp in other cell types has been shown to have dierenoal funcoons than whole cell camp. I hypothesize that camp in the cilium is necessary and sucient to induce adipogenesis in preadipocytes, and that a suite of ciliary gpcrs acts to inuence this process in a cilia-dependent manner. My RST aim will dene the role of ciliary camp in adipogenesis, using chemogeneoc and optogeneoc tools to control the generaoon or depleoon of ciliary camp during adipogenesis to dene its suciency and necessity in preadipocyte dierenoaoon. My second aim will idenofy gpcrs that localize to preadipocyte cilia and invesogate their physiological roles in adipose expansion and prevalence in healthy versus unhealthy adipose ossues. This work will be conducted at the university of utah under the guidance of my sponsor, DR. Keren hilgendorf, and CO- sponsor, DR. Jeremy reiter, both of whom specialize in ciliary signaling. My thesis commiee is composed of interdisciplinary researchers with a range of specialoes all pertaining to dierent poroons of this proposal, such adipose ossue, signaling metabolites, gpcrs, and primary cilia signaling. Together, these mentors will provide expert guidance in all facets of this project. In addioon, this project will be supported by the work of mulople university core facilioes, including those that OER services in cellular microscopy, OW cytometry, mass spectrometry, and metabolomics. These facilioes OER excellent support and training services to facilitate my growth as a researcher. The training plan presented was developed to ulomately prepare me for a future in academia as an independent researcher in the ELD of ciliary signaling and cell fate determinaoon. In addioon to the technical skills this project will provide, IT will also further my development as a mentor and teacher through university-supported training programs and laboratory opportunioes. DR. Hilgendorf has fostered a supporove research environment that encourages scienoc exploraoon and my development as a researcher. She has demonstrated dedicaoon to my training and catered her mentorship to reect my career goals.