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Obesity and Diabetes
1. “Explain why parabiosis of a lean control and an ob/ob mouse caused partial normalization of the body weight in ob/ob mutant mouse?”
The parabiosis of an ob/ob mouse and lean mouse results in:
Increase weight gain in ob/ob mouse
Decrease food uptake of pair
Increase survival of pair for months
The above mentioned effects appear due to the production of a factor named as Leptin that is produced by normal mouse but in a very low concentration that is not sufficient for the body. The ob/ob mouse has receptors to attach this factor but as the amount of leptin is very low, as compared to db/db mutant mouse, it results in the normalization of body weight in ob/ob mutant mouse.
2. “What is the effect on body weight and blood glucose of db/db mutant mouse that went parabiosis with an ob/ob mutant mouse? Why?”
When db/db mouse is parabiosed with ob/ob mouse, it results in increased adipose tissue mass, increased body weight, elevated blood sugar level and GIT distended with food particles. The mutation in db mouse creates significant obesity and hyperphagia, and weight is increased as 30 gm in comparison with 20 gm in ob mouse. The db mutation is located on chromosome 4 as compared to ob mutation, which is located on chromosome 6. The db/db mouse produce a significant level of blood borne satiety factor, leptin. The receptors for leptin are located in hypothalamus part of brain, db/db genes encode the leptin receptors and leptin is produced in adipose tissues; ultimately leading to the above mentioned effects.
3. “Wild type and diabetic (ob/ob and db/db) mice were treated with leptin in the drinking water (10 mg/kg for 4 weeks). Using this regiment, briefly describe the effects on food intake, body weight and blood glucose.”
When leptin is administered to ob/ob and db/db mouse, significant variations are observed. In this case, the db/db mutation is maintained in C57BL/Ks (chromosome 4) and ob/ob mutation in C57BL/6 (chromosome 6). These genes mediate common metabolic pathways in mouse.
The ob/ob mouse shows decrease blood sugar level, decrease food intake, decrease adipose tissue mass, decrease insulinemia and ultimately starvation level is reached and survival time is 20-30 days. And db/db mouse shows increase in body weight and increase in adipose tissue mass. The body mass of db/db mouse will markedly increase up to 50% as compare to ob/ob mouse.
4. “Why the db/db mice may be defective in their ability to respond to leptin?”
The db/db and ob/ob mutant mouse have capability to produce a factor (leptin) in the body but the difference is that db/db mutant mouse overproduces the leptin while normal mouse produces insufficient amount of leptin, which is lethal for the body. Body must have functional receptors to attach leptin for proper response. The db/db mutant mouse has defective receptors for leptin attachment in hypothalamus. As adipose tissues make leptin, and leptin receptors are located in hypothalamus, which becomes hyperphagic due to increase adipose tissue mass resulting in increased leptin production. Increased adipose tissue mass may cause hurdle for attachment of leptin to receptors and also leptin may not be able to cross properly the adipose tissues, so this could be the reason that receptors are unable to give proper response.
5. “Do you support the use of leptin therapy in the clinic for management of obesity? Why?”
No, leptin therapy is not considered to control the obesity in community. For any therapy, to manage the diseased condition, primary consideration is the safety level of the drug/therapy. As leptin produces drastic changes in body in the form of side effects such as immunity is compromised by leptin, which can lead to any pathogen/antigen to grow and attack easily the body. So this therapy is not considered for patients to control obesity.
6. “Some patients harbor mutation that leads to the formation of truncated form of leptin. What could be the unusual adverse effects following the administration of leptin for several months. What are the impacts of these side effects on the interpretation of therapy?”
In normal cases, a very low amount of leptin is produced in the body, but in mutant case increased leptin production increase adipose tissue mass, increase body weight and decrease blood sugar level. Ultimately, energy level would be decreased and body would not respond properly to functions. Immune system is also affected as cytokines Th2 and Th1 will effect antibody production against any virulent antigen.
7. “What did you find most interesting or difficult?”
The most difficult thing is always most interesting i.e Parabiosis. It can be used to study various therapeutic patterns for certain disease management, to check side effects of drugs in paired partners, to monitor adverse effects, to control the immunization as antigen-antibody reactions, to observe normal physiological functions, and to assist in transplantation of body organs.
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