Muscle wasting and protein loss occur during starvation. The loss of more than one third of the body's protein is incompatible with survival. Man, as well as the rat, has developed a series of metabolic maneuvers designed to spare body protein during prolonged starvation. This is in large part accomplished by a preferential use of fat as fuel resulting in sparing the body protein and maintenance of muscle mass. In the rat, we have evidence to believe that muscle is the only tissue to adapt to starvation to conserve protein, and adaptation lost when lipid stores become exhausted. The overall objective of this proposal is to delineate the mechanism(s) by which protein in muscle is conserved during starvation. It is our hypothesis that the availability of lipid fuels is associated and responsible for protein sparing. To detemine the basis for this relationship, we propose to use the normal and fat-red rat model we have developed and to employ the use of intact rats, the perfused rat hindquarter and incubated muscles. These studies are designed to evaluate protein synthesis and degradation in muscle and have the following specifc aims: (1) To characterize the hormonal and fuel pattern of the fat-fed rat during starvation and to correlate these to changes in muscle fuels and proteinases. (2) To show that protein conservation is associated with the availability of lipid fuels. We intend to show that interferring with lipid metabolism during protein conservation results in protein loss from muscle. (3) To assess which factors trigger the augmented protein loss when lipid stores become exhausted. Using the perfused hindquarter we will evaluate the role of lipid fuels, the redox state, prostaglandins, leucine and calcium. (4) To assess the role of insulin and glucocorticoids in protein conservation. In these studies we intend to measure the binding of insulin and corticosterone to muscle in starved rats as well as in rats treated with various agents that interfere with lipid metabolism. Lastly, (5) we intend to assess the physiochemical properties of a serum factor from fasted rats that we have shown can modulate protein metabolism in muscle.
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