Zebrafish are hot - these little fish are all the rage in the research world these days. They develop very quickly (embryo to fish in just a couple of days) and scientists are developing better ways to manipulate their genes and use them to study human disorders. Obviously, fish are pretty different than humans, but surprisingly many pathways are well conserved across the species.In a new paper by scientists at Oregon Health and Science University [see press release and article , including a picture of a fat fish] the authors found that the melanocortin pathway, a central pathway critical to regulating appetite and weight gain in mammals, is also present and functional in zebrafish. The neuropeptide AgRP, which increases appetite and feeding in mammals, and the members of the melanocortin receptor family, including MC3-R, MC4-R and MC5b-R are all present and act in a similar manner in zebrafish as in man. The researchers show that zebrafish with an overactive AgRP gene get big and fat, with much larger fat cells (adipocytes) than normal fish. This study, along with several others investigating known appetite controlling proteins in fish, pave the way for using these fish to better understand how genes and the environment regulate energy intake and metabolism.
One excellent aspect of zebrafish is that you can grow them in large numbers and use them for screening drugs. So, you could take these transgenic zebrafish, with the appetite regulating gene(s) disrupted, and then try a huge panel of compounds to see what makes them thin (this can be done by growing the fish in compartments that each have one compound added to the water). For example, another recent study screened 16,320 different compounds using zebrafish embryos to identify new molecules that can stop cells from dividing (and might be useful for cancer therapy).
The possibilities for using these fish to better understand the causes and possible treatments for obesity are far reaching.
Theresa Strong
Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.
