New aspects of ketone bodies in energy metabolism of dairy cows: a review.

Increased lipolysis, low insulin/glucagon ratios and malonyl-CoA concentrations are prerequisites for ketogenesis. From an aetiological viewpoint, there are two quite different types of metabolic disorders in which ketosis can occur, the hypoglycaemic-hypoinsulinaemic and the hyperglycaemic-hyperinsulinaemic type. The former, Type I, generally occurs 3-6 weeks after calving in cows whose milk secretion is so extensive that the demand for glucose exceeds the capacity for glucose production. To protect the body from hazardous protein degradation by a high rate of gluconeogenesis, this process is inhibited and the increased energy requirements are met by the elevated utilization of ketone bodies. In this strong catabolic metabolic state the plasma levels of glucose and insulin are very low, the levels of ketone bodies are high and there are small risks for fat accumulation in the liver cells. The hyperglycaemic, hyperinsulinaemic form, Type II, generally occurs earlier in lactation. An important aetiologic factor is overfeeding in the dry period, which can lead to disturbances in the hormonal adaptation of metabolism at calving with increased plasma levels of insulin and glucose and often out not always also with hyperketonaemia. If combined with stress, there may be increased lipolysis in adipose tissues, lipid synthesis and accumulation in the liver, i.e. the development of fatty liver. This hyperglycaemic form of disturbance has many similarities with the initial stage of non-insulin-dependent (Type II) diabetes in humans. It has been shown that ketone bodies inhibit protein degradation and thereby gluconeogenesis and also are able to spare glucose by inhibiting glucose utilization. They also can inhibit lipolysis and function as a regulatory safety system, replacing insulin, in situations when the activity of this hormone is low, as in Type I ketosis. Ketone bodies thus have important functions as substrates replacing glucose in many tissues and also as signal substances in the regulation of energy metabolism.