Enterostatin/Procolipase

Abstract

Man is constructed to eat regular meals. Moreover, man is constructed to prefer food that is energy-rich and tasty. Dietary lipids are both energy-rich and tasty, with several spices being lipid soluble. In the early history of man dietary lipids were scarce but gradually increased with the development of an agricultural society. Since the 1950s dietary fat intake in the Western world has dramatically increased from around 30 energy percent to 40 energy percent (Dreon et al., 1988). This has as a consequence an increased frequency of obesity and insulin resistance, eventually leading to Type 2 diabetes at the moment of failure of the islets of Langerhans (Bray et al., 1990; Steffens et al., 1991; Shafrir and Gutman, 1993). The reason that a high fat intake has serious metabolic implications is that fat taken in is not automatically oxidized in proportion to its consumption as is dietary carbohydrate and protein (Thomas et al., 1992). Instead an increased fat intake leads to the accumulation of fat in skeletal muscle and adipose tissue. The insulin resistance following high-fat feeding is due to an impairment of the insulin receptor signaling events downstream in the target cell, the insulin receptor and its insulin receptor substrates, for instance Insulin receptor substrate 1 (IRS-1) and Phosphatidylinositol-3 kinase (PI3-kinase), being phosphorylated at several serine/threonine residues instead of the normal tyrosine phosphorylation (Paz et al., 1996). In the muscle that is the first tissue to become insulin resistant following high-fat feeding, long-chain acyl-CoA has been shown to raise the levels of protein kinase C, which in turn activates serine/threonine residues (Schmitz Peiffer et al., 1997). In light of the multiple metabolic disturbances of a high dietary fat intake, great interest has been taken in the regulation of appetite, especially with the interest of a specific macronutrient appetite regulation.