Integrated metabolic control of food intake after 2-deoxy-D-glucose and nicotinic acid injection

Abstract

We measured the minute-to-minute respiratory quotient (RQ), total metabolic rate, and the intensity and energy cost of locomotor activity in unrestrained rats with a recently developed open-circuit metabolic device. These measures permitted calculation of the resting metabolic rate (designated métabolisme de fond or MF). Simultaneous monitoring of the meal patterns of the animals allowed correlations between MF and feeding behavior. The major hypotheses proposed to account for the onset of feeding were challenged by pharmacological inhibition of the utilization of glucose and/or lipids. When injected together, 2-deoxy-D-glucose, which blocks glucose utilization, and nicotinic acid, which blocks lipid utilization, had a synergistic effect on MF and on the feeding response. The RQ, which reflects the relative rate of glucose-to-lipid utilization, showed that neither the inhibition of utilization of glucose nor the inhibition of utilization of lipids could account for the magnitude of the feeding response. The signal that best accounted for these examples of experimentally induced feeding is ischymetric (power or rate of energy) in nature rather than solely glucostatic or solely lipostatic.

Nicotinic acid promotes sleep through prostaglandin synthesis in mice

“…In fact, metabolic heat production (VO 2 ) was suppressed in response to nicotinic acid in our study. Consistent with our finding, 200 mg/kg nicotinic acid attenuates cold-induced increases in thermogenesis in mice 52 and norepinephrine-induced 53 or spontaneous 54 thermogenesis in rats. A major factor contributing to decreased thermogenesis is suppressed feeding in mice.…”

Metabolic and glucostatic control of feeding

“…This synergism was observed at doses of the two agents that alone did not increase food intake , indicating that sub-threshold changes in glucose and fatty acid oxidation combine to stimulate feeding. Similar results were obtained with combined administration of 2-DG and nicotinic acid, which blocks fat mobilization (Even et al 1988). In addition, parenterally-and intragastrically-administered glucose proved to be more satiating when the rate of fatty acid oxidation was high (Geary et al 1979).…”

Ingestive homeostasis: The primacy of learning.

“…More contemporary versions of hypotheses based on the same principles are those of Friedman, Tordoff, and Ramirez (1986) and of Even and Nicolaidis (1985;Even, Coulaud, & Nicolaidis, 1988). Rather than focusing on a single nutrient or energy source such as glucose or stored fat as the sole determinant of the critical error signal, they contended that energy usage, as reflected in some critical organ such as the liver or the brain, is what is important and that it is independent of the actual fuel or fuels being utilized.…”