Can studying fat in fish help us to come to grips with obesity?


Humans are born with both brown and white fat deposits in typical locations in the body.  The function of brown fat is to generate heat and it diminishes in early childhood.  White fat plays three primary roles: energy storage, insulation from adverse temperature and hormone secretion. In children, white fat depots grow by increasing the number and size of fat cells (called adipocytes).  In adults although individual adipocyte die and are replenished, the number of adipocytes is remains constant.  Mature adipocytes do not divide, and new adipocytes are thought to be generated from precursor cells found in fat deposits. We know that differentiation of adipocytes involves a many genes.  However, we have a very poor understanding of how fat deposits are initially established in different areas of the embryo.



This zebrafish is transparent except for the eyes.  A red dye is used to detect where fat has been deposited.




Why study embryonic fat development? 

We know that the foetal environment provided by the mother to the embryo has lasting effects on health.  Hormonal and nutritional levels can predispose children to be obese, and there is a strong genetic link to obesity.  Obesity causes a higher incidence of type 2 diabetes and heart and vascular problems.  These obesity related conditions are linked most closely to the presence of excess visceral fat which forms around the gut and confers a round body  fat shape.  Excess subcutaneceous fat in the thighs and buttocks (the so called pear-shaped body) is much less risky.  Fat is deposited in both of these areas in the embryo.  So by understanding how the to different types of deposit are established in the embryo, we may be able to affect their activity in the adult and reduce the "bad" form of fat deposition.


Zebrafish as a model for fat development.

Although zebrafish are a small tropical fish,  we know that fat develops in much the same way as in humans.  Because the eggs are fertilised outside of the mother, we can obtain embryos easily without harming the mother.  Zebrafish are relatively easy to keep and inexpensive. There are hundreds of laboratories worldwide that study different biological questions, thus there are many techniques and tools to aid in zebrafish research.  We feel that zebrafish is one of the best tools to study fat development.  One of our recent studies found that a gene called PPAR-gamma and the nutrient vitamin A (retinoic acid) work together to encourage precursor cells to become adipocytes.  Some of the question that we intend to answer now are:   What are the conditions that stimulate fat growth in the embryo?  Do blood vessels play a role?  Does the embryo have to have soluble fat circulating in the blood before adipocytes form?  What are the genes involved in fat development.  By answering these questions we will shed light on the earliest stages of adipocyte differentiation and begin to understand why the location of fat deposits vary between different individuals.


Further reading:

-   Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways.

-   Tackling Obesities:  Future Choices – Project report

 

Roehl Lab