33 research outputs found
Inhibitory effects of halothane on the thermogenic pathway in brown adipocytes: localization to adenylyl cyclase and mitochondrial fatty acid oxidation
Volatile anesthetics such as halothane efficiently inhibit nonshivering thermogenesis as well as the cellular manifestation of that phenomenon: norepinephrine-induced respiration in brown adipocytes. To identify the molecular site(s) of action of such anesthetics, we have examined the effect of halothane on the sequential intracellular steps from the interaction of norepinephrine with isolated brown adipocytes to the stimulation of mitochondrial respiration (=thermogenesis). We did not identify an inhibition at the level of the adrenergic receptors, but a first site of inhibition was identified as the generation of cAMP by adenylyl cyclase; this led to inhibition of norepinephrine-induced expression of the uncoupling protein-1 (UCP 1) gene and reduced norepinephrine-induced lipolysis as secondary effects. Although an inhibition of lipolysis in itself would inhibit thermogenesis, circumvention of this inhibition revealed that a second, postlipolytic, site of inhibition existed: halothane also inhibited the stimulatory effect of exogenous fatty acids on cellular respiration. This inhibition was independent of the presence of UCP1 in the mitochondria of the cells and was thus not directly on the thermogenic uncoupling mechanism. Since not only fatty acid oxidation but also pyruvate oxidation were inhibited by halothane in isolated mitochondria, whereas glycerol-3-phosphate oxidation was not, the second site of action of halothane, evident when cyclase/lipolytic inhibition was circumvented, was located to the respiratory chain, complex I. The results thus explain the inhibition of nonshivering thermogenesis by identifying two sites of action of halothane in brown adipocytes. In addition, the results may open for new formulations of the molecular background to anesthesia. (C) 2004 Elsevier Inc. All rights reserved
Impact after three years of the Swedish energy audit program
The Swedish energy audit program is a publicly financed program, mainly targeting small and medium-sized firms to help them finance energy audits. By examining suggested and implemented energy efficiency measures from the energy audits conducted in 241 firms in the program, the aim of this paper is to examine the energy efficiency implementation gap and the cost efficiency of the program. The autis show that the firmsâ average annual energy efficiency improvement potential is between 860 and 1270 MWh/year which corresponds to a total energy efficiency improvement potential of between 6,980 -11,130 MWh / firm. The implementation rate of the suggested energy efficiency improvement measures in the SEAP is 53%. The program has resulted in investments in energy efficiency improvements between ⏠74,100- ⏠113,000 / firm
Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARgamma) function.
Mice with a dominant-negative peroxisome proliferator-activated receptor gamma
(PPARgamma) mutation (P465L) unexpectedly had normal amounts of adipose tissue.
Here, we investigate the adipose tissue of the PPARgamma P465L mouse in detail.
Microscopic analysis of interscapular adipose tissue of P465L PPARgamma mice
revealed brown adipocytes with larger unilocular lipid droplets, indicative of
reduced thermogenic capacity. Under conditions of cold exposure, the brown
adipose tissue of the PPARgamma P465L mice was less active, a fact reflected in
decreased uncoupling protein 1 levels. Analysis of the white adipocytes confirmed
their normal cytoarchitecture and development, yet classical white adipose depots
of the P465L PPARgamma mice had a striking reduction in brown adipocyte
recruitment, a finding supported by reduced expression of UCP1 in the perigonadal
adipose depot. Taken together, these data suggest that whole animal impairment of
PPARgamma alters the cellular composition of the adipose organ to a more "white"
adipose phenotype. Physiologically, this impairment in brown adipocyte
recruitment is associated with decreased nonshivering thermogenic capacity after
cold acclimation as revealed by norepinephrine responsiveness. Our results
indicate that maintenance of oxidative brown-like adipose tissue is more
dependent on PPARgamma function for development than white adipose tissue, an
observation that may be relevant when considering PPARgamma-dependent strategies
for the treatment of obesity