Feeding regulation by endogenous sugar acids through hypothalamic chemosensitive neurons.
Analysis of blood of fasted rats revealed two endogenous sugar acids, 3,4-dihydroxybutanoic acid (2-deoxytetronic acid; 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid; 3-DPA), that might be related to food intake control. Injection of 2-DTA into the third cerebral ventricle reduced food intake for 24 hr in 72 hr deprived rats and depressed single neurons activity in the lateral hypothalamus (LHA). The same amounts of 3-DPA elicited feeding in a dose-related fashion, and increased LHA single neuron activity with 6 to 8 min latency. Intravenous injection of 3-DPA, but not 2-DTA, was effective. Liposome encapsulation of 2-DTA enhanced its potency after intraperitoneal injection, probably by allowing passage across the blood-brain barrier. Electrophoretic application of 2-DTA significantly and specifically suppressed, and 3-DPA facilitated activity of glucose-sensitive (GS) neurons in the LHA. Neither affected glucose insensitive LHA neurons. Both sugar acids affected glucoreceptor (GR) neuron activity oppositely in the ventromedial hypothalamic nucleus (VMH). Intracellular recordings verified that the effect of 2-DTA on the GS and GR neurons was the same as glucose. Hyperpolarization of GR neurons with a membrane conductance increase was brought about by 3-DPA. The levels of plasma glucose and insulin changed oppositely by 2-DTA and 3-DPA, respectively when these were applied into the third cerebral ventricle. Feeding behavior and LHA and VMH neuron activity changes after injection suggest 2-DTA may be an endogenous satiety substance and 3-DPA a hunger substance, with effects mediated by GS neurons in LHA and GR neurons in VMH. Effects of 3-hydroxybutyric acid were also verified and discussed.
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006885:Hydroxybutyrates / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D011919:Rats, Inbred Strains; D013400:Sugar Acids / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D013400:Sugar Acids; C041038:3,4-dihydroxybutanoic acid; C041039:3-deoxypentonic acid; D020155:3-Hydroxybutyric Acid