Role of malonyl-CoA in the hypothalamic control of food intake and energy expenditure.

The brain plays an important role in the regulation of energy balance in higher animals. Global energy balance is monitored by sets of neurons in the hypothalamus that respond to peripheral hormonal and afferent neural signals that sense the energy status. Malonyl-CoA, an intermediate in the biosynthesis of fatty acids, appears to function in this hypothalamic energy-sensing system. The steady-state level of malonyl-CoA is determined by its rate of synthesis catalysed by ACC (acetyl-CoA carboxylase) relative to its rate of turnover catalysed by FAS (fatty acid synthase). Changes in the level of malonyl-CoA in the hypothalamus alter the expression/secretion of key hypothalamic orexigenic and anorexigenic neuropeptides that regulate the feeding behaviour and energy expenditure. Inhibitors of FAS, administered i.c.v. (intracerebroventricularly) to lean or obese mice, cause a rapid rise in hypothalamic malonyl-CoA level, suppression of food intake, increased fatty acid oxidation in skeletal muscle and profound weight loss. Stereotactic delivery of a viral MCD (malonyl-CoA decarboxylase) expression vector into the ventral hypothalamus lowers malonyl-CoA levels and reverses the anorectic effect of the FAS inhibitors. Fasting decreases, whereas refeeding increases, hypothalamic malonyl-CoA and alters subsequent feeding behaviour accordingly. The level of malonyl-CoA in the hypothalamus appears to be under the control of 5'-AMP kinase, which phosphorylates and thereby inactivates ACC under conditions of energy surplus. Thus malonyl-CoA appears to link the energy-responsive fatty acid synthesis in the hypothalamus to feeding behaviour and peripheral energy expenditure.

Experimental analysis of fluid mechanical energy losses in aortic valve stenosis: importance of pressure recovery.

Current methods for assessing the severity of aortic stenosis depend primarily on measures of maximum systolic pressure drop at the aortic valve orifice and related calculations such as valve area. It is becoming increasingly obvious, however, that the impact of the obstruction on the left ventricle is equally important in assessing its severity and could potentially be influenced by geometric factors of the valve, causing variable degrees of downstream pressure recovery. The goal of this study was to develop a method for measuring fluid mechanical energy losses in aortic stenosis that could then be directly related to the hemodynamic load placed on the left ventricle. A control volume form of conservation of energy was theoretically analyzed and modified for application to aortic valve stenosis measurements. In vitro physiological pulsatile flow experiments were conducted with different types of aortic stenosis models, including a venturi meter, a nozzle, and 21-mm Medtronic-Hall tilting disc and St. Jude bileaflet mechanical valves. The energy loss created by each model was measured for a wide range of experimental conditions, simulating physiological variation. In all cases, there was more energy lost for the nozzle (mean = 0.27 J) than for any other model for a given stroke volume. The two prosthetic valves generated approximately the same energy losses (mean = 0.18 J), which were not statistically different, whereas the venturi meter had the lowest energy loss for all conditions (mean = 0.037 J). Energy loss correlated poorly with orifice pressure drop (r2 = 0.34) but correlated well with recovered pressure drop (r2 = 0.94). However, when the valves were considered separately, orifice and recovered pressure drop were both strongly correlated with energy loss (r2 = 0.99, 0.96). The results show that recovered pressure drop, not orifice pressure drop, is directly related to the energy loss that determines pump work and therefore is a more accurate measure of the hemodynamic significance of aortic stenosis.

The need of eccentric balance during mastication.

A study of the masticatory performance of 30 patients with balancing contacts in centric relation was compared with an equal number of patients with balancing contacts in both centric and eccentric relations. The study failed to show any significant difference between masticatory performance of the two groups.