Dopaminergic Control of Ketogenesis in Fasting

Abstract

The role of dopamine in starvation ketonaemia was investigated in male Wistar rats by administration of a specific dopamine receptor antagonist, metoclopramide (4 mg . kg-1 . 24h-1), or placebo, intragastrically during a 48-h fast. Starvation alone caused a fall in blood glucose and gluconeogenic precursor concentrations, which was unaffected by metoclopramide administration. Circulating 3-hydroxybutyrate and acetoacetate levels rose with fasting alone but metoclopramide impaired this ketonaemic response. After 48-h starvation, total ketone body concentrations (mean +/- SEM) were 2.28 +/- 0.19 mmol/l with metoclopramide therapy, 3.49 +/- 0.21 mmol/l with placebo, P less than 0.001. Plasma non-esterified fatty acid levels were similar in metoclopramide- and placebo-treated animals, as were circulating concentrations of insulin, glucagon and growth hormone. Metoclopramide thus decreased the ketonaemic response to starvation without an apparent change in lipolysis or circulating hormone levels, suggesting a direct role for dopamine in production of starvation ketonaemia.

Serum levels of β-hydroxybutyrate and pyruvate, metabolic changes and cognitive function in patients with schizophrenia during antipsychotic treatment: a preliminary study

“… 34 Among them, a postsynaptic dopamine receptor antagonist could reduce ketonemia in a state of starvation. 35 Aripiprazole is an atypical antipsychotic with partial agonist activity at dopamine D 2 and serotonin 5 HT 1A receptors, as well as being antagonistic at 5-HT 2A receptors. 36 Changes in β-HB are primarily observed in the AZ group; however, this finding cannot be explained by the previous finding that dopamine antagonist reduces ketonemia, which may hint that neurotransmitter dopamine may be involved in the energy utilization process but cannot explain the entire mechanism.…”

Dopamine in the pituitary adaptation to starvation in man

“…It has been recently suggested that starvation might enhance peripheral dopaminergic activity as dopamine receptor blockade decreased the total ketone body levels in fasted rats (Belsa-Malpica et al, 1981). However, this may not apply to man or necessarily to all peripheral tissues in animals for the following reasons.…”