Obesity Studies using rats

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Rats have been used in science since around the year of 1857. "Norway rats" were caught and bred until an albino strain was established to be used for research. Rats have been used for models of human reproduction, endocrine function, nutrition, and cancer. Rats are more similar to humans in vascular physiology making them candidates for clinical research. Rats are generally chosen over mice in studies correlating to human health because they are easier to anesthetize and more blood can be taken for analysis. Laboratory rats have been bred to be calmer, less likely to bite, tolerate crowding better, and produce more offspring. These qualities make then excellent for living in the laboratory setting. Interestingly, rats are not usually genetically modified, but bred until a particular trait is shown. This allows researchers to study a specific condition, such as obesity, without being effected by the genetic difference. However, transgenic rats do exist for research purposes.

The Zucker rat is often used in studies involving obesity. Two forms of the Zucker rat exist; a fatty Zucker and a lean Zucker. The fatty Zucker rat is homozygous recessive (fa/fa) and can weight up to 1 kilogram (2.2 lbs). The lean Zucker is either homozygous dominant (Fa/Fa) or heterozygous (Fa/fa) and represents a normal lab rat. Zucker rats are named after Lois and Theodore Zucker, who were pioneers in the study of obesity.

The driving force behind the extreme weight gain of a fatty Zucker rat is the hyperphagic nature of the rat. The recessive allele leads to a dysfunctional leptin receptor in the hypothalamus of the brain. Leptin is a hormone that is released from adipocytes. The amount of leptin released in the blood is proportional to the amount of fat in the body. When it reached the hypothalamus, hunger suppressors are released and feeding stimulants are sequestered. Without a functional leptin receptor, the leptin never binds, and the rat never feels full.

Obesity Zucker rats are noticeably obese by 3 to 5 weeks and have a body composition of over 40% lipids by the fourteenth week. These obese rats have high levels of lipids and cholesterol in their blood and are resistant to insulin. However, they are not hypoglycemic. An increase in size is due to an increase in the amount and size of adipose cells in the body. Zucker fatty rats are plagued with diabetes, abnormal heart function, and decreased sympathetic nervous system responses. Cardiomegaly, or enlargement of the heart, is also observed in the autopsy of a fatty Zucker rat as a result of ventricular hypertrophy. When the myocytes were observed, fatty Zucker rats showed hypertrophic myoctyes and a reduction in the amount of connective tissue between cells, a sign of stress on the heart.