Final answer:
Insulin resistance leads to increased lipolysis and elevated free fatty acid release because of the weakened inhibitory effect of insulin on hormone-sensitive lipase. This condition is associated with metabolic disorders and can be exacerbated by metabolic acidosis, which impairs the insulin signaling pathway.
Step-by-step explanation:
Insulin resistance affects the regulation of lipolysis and the release of free fatty acids (FFA). Normally, insulin inhibits hormone-sensitive lipase, an enzyme that breaks down triglycerides into glycerol and FFA in adipose tissue. When cells become resistant to insulin, this inhibition weakens, leading to an increase in lipolysis and a higher level of circulating FFA. Elevated levels of FFA in the blood are associated with various metabolic disorders, such as type 2 diabetes and metabolic syndrome. Furthermore, insulin resistance can impair glucose uptake and metabolism, as insulin stimulates the translocation of the Glut-4 transporter to the plasma membrane, which in turn increases glucose intake and glycogen synthesis, while promoting glycolysis and fatty acid synthesis.
In the context of metabolic acidosis, insulin resistance can be further aggravated. Metabolic acidosis may damage the insulin signaling pathway, through inhibition of the phosphoinositide 3-kinase (PI3K) activity and its downstream effectors, particularly in skeletal muscle. This can hinder insulin's antiproteolytic effect, which can lead to decreased lean body mass in chronic conditions. Moreover, metabolic acidosis can lead to an increase in glucocorticoid secretion and plasma cortisol levels, further contributing to insulin resistance and its associated metabolic complications.