Key Words Liraglutide • 3T3-L1 preadipocytes • Adipogenesis • FASN AbstractBackground/Aims: The aim of this study was to determine the direct role of liraglutide (LG) in adipogenesis and lipid metabolism. Methods: Lipid accumulation was evaluated by oil red O staining, quantitative real-time PCR (qPCR) was performed to determine glucagon-like peptide 1 receptor (GLP-1R), fatty acid synthase (FASN) and adipose triglyceride lipase (ATGL) expression in 3T3-L1 preadipocytes, differentiated adipocytes and in adipose tissues from mice. The effects of LG on 3T3-L1 adipogenesis and lipid metabolism were analyzed with qPCR, Western Blotting, oil red O staining, immunohistochemistry (IHC) and immunofluorescence (IF). All measurements were performed at least three times. Results: LG increased the expression of differentiation marker genes and lipid accumulation during preadipocyte differentiation. In differentiated adipocytes, LG decreased FASN expression, and simultaneously led to CREB phosphorylation and ERK1/2 activation which were abolished by a GLP-1R antagonist, exendin (9-39).LG induced-FASN down-regulation was partially reversed by PKA and ERK1/2 inhibitors. Consistent with above in vitro findings, LG treatment significantly reduced FASN expression in visceral adipose tissues of ob/ob mice, and reduced body weight gain. Conclusion: LG promotes preadipocytes differentiation, and inhibits FASN expression in adipocytes.LG induced down-regulation of FASN is at least partially mediated by PKA and MAPK signaling pathways.

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We investigate the heat transport between two nonthermal reservoirs based on a microscopic collision model. We consider a bipartite system consisting of two identical subsystems, and each subsystem interacts with its own local reservoir, which consists of a large collection of initially uncorrelated ancillas. Then a heat transport is formed between two reservoirs by a sequence of pairwise collisions (intersubsystem and subsystem-local reservoir). In this paper we consider two kinds of the reservoir's initial states: the thermal state and the state with coherence whose diagonal elements are the same as that of the thermal state and the off-diagonal elements are nonzero. In this way, we define the effective temperature of the reservoir with coherence according to its diagonal elements. We find that for two reservoirs having coherence the direction of the steady current of heat is different for different phase differences between the two initial states of two reservoirs, especially the heat can transfer from the "cold reservoir" to the "hot reservoir" in the steady regime for particular phase difference. In the limit of the effective temperature difference between the two reservoirs ΔT→0, for most of the phase differences, the steady heat current increases with the increase of effective temperature until it reaches the high effective temperature limit, while for the thermal state or particular phase difference the steady heat current decreases with the increase of temperature at high temperatures, and in this case the conductance can be obtained.

To identify alcohol-responsive brain areas, we have immunohistochemically analyzed expression of c-Fos, FosB, and other Fos-related antigens in the brain of inbred DBA/2J mice after a single or repeated injection of alcohol (4 g/kg). We observed increased expression of c-Fos after alcohol administration in the central nucleus of amygdala, paraventricular nuclei of hypothalamus and thalamus, and several other brain areas. Although increased expression of c-Fos in the nucleus accumbens was also observed, this increase was not statistically significant. Repeated administration of alcohol had the tendency to reduce alcohol-induced c-Fos expression in these areas. Immunohistochemical analysis using an antibody recognizing most Fos-related antigens revealed increases of expression of these proteins in a partially overlapping set of brain regions. In contrast to c-Fos, FosB expression was found to be elevated significantly higher after repeated than after acute treatment with alcohol in several brain areas, including the shell of nucleus accumbens. In contrast to previous c-Fos studies, our studies confirm that alcohol administration indeed activates the reward circuits, including the basal ganglia, and suggest that FosB could serve as a more sensitive marker for this activation.

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