Instructions

Leptin is an adipokine, a peptide hormone secreted by adipose tissue. It plays a major role in coordinating response systems linking the nutritional state of the body to environmental signals. For example, if the environment provides enough food, the body will build up fat reserves (triacylglycerols, or TAGs). The adipocytes release leptin, resulting in inhibition of food intake and increased energy expenditure. In 1949. an obese strain of mice was established that possessed a mutation mapping to mouse chromosome 6. Mice that were homozygous for the mutation (ob/ob) were obese. In 1994. Jeffrey Friedman and colleagues characterized the OB gene and later isolated the product of the gene, a protein of 167 amino acids (designated leptin) that is exclusively produced in adipose tissue. What is the likely reason that oblob mice are obese? They cannot synthesize melanocyte-stimulating hormone (MSH). They do not respond to neuropeptide Y (NPY). 167 amino acids (designated leptin) that is exclusively produced in adipose tissue. What is the likely reason that oblob mice are obese? They cannot synthesize melanocyte-stimulating hormone (MSH). They do not respond to neuropeptide Y (NPY). They lack leptin receptors. They do not produce leptin. MSH secreted in response to leptin suppresses appetite and increases metabolism. However, animals without the MSH precursor have increased metabolism and increased appetite. In a 2001 experiment by Stacy Forbes and colleagues, oblob mice were injected daily with one of the following: • leptin • MSH 3.88 in grams after 10 days 2.88 5.72 3.88 Weight gain in grams after 10 days 2.88 MSH secreted in response to leptin suppresses appetite and increases metabolism. However, animals without the MSH precursor have increased metabolism and increased appetite. In a 2001 experiment by Stacy Forbes and colleagues, oblob mice were injected daily with one of the following: • leptin • MSH • MSH + leptin • control, injected with vehicle (buffered saline) only, no hormone The mice were allowed to eat at will. The plot shows the average weight gain for each group after 10 days. (Treatments, from left to right are: control, MSH. leptin + MSH, and leptin.) How much more weight did the control mice gain than the mice treated with MSH only? That is what is the difference in weight gain between the control mice and those treated with MSH only? 2.78 Treatments Data from Forbes et al. (2000) Proc Natl Acad Sci 97): 4233-4237 control, MSH, leptin + MSH, and leptin.) o Treatments Data from Forbes et al. (2001) Proc Natl Acad Sci 98(7): 1233-4237. How much more weight did the control mice gain than the mice treated with MSH only? That is, what is the difference in weight gain between the control mice and those treated with MSH only? weight gain difference: Which two of the choices could also cause obesity in a mouse model? inhibiting NPY activity administering MSH to a normal mouse overexpressing the MSH receptor on NPY neurons inhibiting leptin transport across the blood-brain barrier knocking out the gene for the leptin receptor

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