Modulation of feeding by endogenous sugar acids acting as hunger or satiety factors

Endogenous sugar acids, 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), have been identified in the serum of fasted rats. Effects of these sugar acids on rat feeding behavior and neuron activity were investigated. Injections of 2-DTA (2.5 mumol) into the third cerebral ventricle of chronic rats suppressed food intake and single-neuron activity in the lateral hypothalamic area (LHA). Food consumption was reduced for 24 h, even in 72-h food-deprived rats. The same amounts of 3-DPA elicited feeding and increased LHA single-neuron activity with latencies of 6-8 min. Electrophoretically applied 2-DTA significantly and specifically suppressed activity of glucose-sensitive neurons in the LHA, whereas 3-DPA facilitated the activity. Nonglucose-sensitive LHA neurons were not affected by these sugar acids. The high correlation between modulation of feeding behavior and changes in LHA neuron activity after injection of these sugar acids suggested that 2-DTA may act as an endogenous satiety substance and 3-DPA as a hunger substance. The effects may be mediated through glucose-sensitive neurons in the LHA.