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Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes carboxylation of acetyl-CoA to form malonylCoA. In mammals, two isozymes exist with distinct physiological roles: cytosolic ACC1 participates in de novo lipogenesis (DNL), and mitochondrial ACC2 is involved in negative regulation of mitochondrial ␤-oxidation. Since systemic ACC1 null mice were embryonic lethal, to clarify the physiological role of ACC1 in hepatic DNL, we generated the liver-specific ACC1 null mouse by crossbreeding of an Acc1 lox(ex46) mouse, in which exon 46 of Acc1 was flanked by two loxP sequences and the liver-specific Cre transgenic mouse. In liver-specific ACC1 null mice, neither hepatic Acc1 mRNA nor protein was detected. However, to compensate for ACC1 function, hepatic ACC2 protein and activity were induced 1.4 and 2.2 times, respectively. Surprisingly, hepatic DNL and malonyl-CoA were maintained at the same physiological levels as in wild-type mice. Furthermore, hepatic DNL was completely inhibited by an ACC1/2 dual inhibitor, 5-tetradecyloxyl-2-furancarboxylic acid. These results strongly demonstrate that malonyl-CoA from ACC2 can access fatty acid synthase and become the substrate for the DNL pathway under the unphysiological circumstances that result with ACC1 disruption. Therefore, there does not appear to be strict compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver.Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, which is a key molecule in the control of intracellular fatty acid metabolism (13,16,27). ACC has two major isozymes that have different physiological roles based on their distinct subcellular distributions (2). A cytosolic enzyme, ACC1 (ACC␣; molecular mass, 265 kDa), supplies malonyl-CoA to fatty acid synthase (FAS) and is committed to de novo lipogenesis (DNL) in many tissues via subsequent nutritional and hormonal regulation (3,16,27). In contrast, ACC2 (ACC␤; molecular mass, 280 kDa) is anchored to the mitochondrial surface via a unique N-terminal domain that includes 20 hydrophobic amino acids (1, 2). ACC2 produces malonyl-CoA on the mitochondrial surface. It is well known that malonylCoA is a potent endogenous inhibitor of carnitine palmitoyl transferase 1 (CPT-1), which is also located on the mitochondrial surface (21, 26). Thus, ACC2 indirectly prevents the influx of fatty acids into the mitochondria and their subsequent ␤-oxidation (4).ACC1 is ubiquitously expressed in many tissues, but higher levels occur in lipogenic tissues, including the liver and adipose tissue (8). In fact, in animals, Acc1 gene expression and ACC activity are markedly induced either by high carbohydrate feeding or hyperinsulinemia in animals and result in increases in adiposity, lipoprotein secretion, and hepatic fat content (16). It is expected that ACC1 blockade should reduce flux through the DNL pathway in lipogenic tissues and thus reduce adiposity, lipoprotein secretion, and fatty liver (11,23). It is therefore plausible that ACC1 inh...

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To clarify the role of the neuropeptide Y (NPY) Y5 receptor subtype in energy homeostasis, the effect of the intracerebroventricular infusion of a selective Y5 agonist, D-Trp(34)NPY, was investigated in C57BL/6J mice. Intracerebroventricular infusion of D-Trp(34)NPY (5 and 10 microg/d) produced hyperphagia and body weight gain, accompanied by increased adipose tissue weight, hypercholesterolemia, hyperinsulinemia, and hyperleptinemia. Oral administration of a selective Y5 antagonist at a dose of 100 mg/kg twice a day completely suppressed all of these D-Trp(34)NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity. In addition, D-Trp(34)NPY still resulted in an increase in adipose tissue weight accompanied by hyperleptinemia and hypercholesterolemia, although D-Trp(34)NPY-induced food intake was restricted by pair-feeding. Under the pair-fed condition, D-Trp(34)NPY decreased hormone-sensitive lipase activity in white adipose tissue and uncoupling protein-1 mRNA expression in brown adipose tissue. These findings indicate that Y5-mediated obesity may involve metabolic changes, such as decreased lipolysis and thermogenesis, as well as hyperphagia. Therefore, the Y5 receptor can play a key role in regulating energy homeostasis.

Chemical imaging techniques such as mass spectrometry (MS) imaging and imaging spectroscopy have grown to be important in a variety of fields. Infrared spectrum information, for example is essential to evaluate organic and biological samples. Recently, near-field spectroscopy techniques have been developed that enable higher spatial resolution above the one usually obtainable due to wavelength limitations. In terms of chemical imaging for organic materials, time-of-flight secondary ion mass spectrometry (TOF-SIMS) is one of the powerful techniques because of extremely high sensitivity and high spatial resolution of approximately 100 nm. Since TOF-SIMS does not always provide complete information on complex samples, a complementary technique of similar spatial resolution is required. Near-field infrared microscope (NFIR) is the most promising candidate for a complementary analysis method along with TOF-SIMS. It is, however, often difficult to interpret NFIR data because of the low signal intensity in near-field infrared. Multivariate analysis techniques such as principal component analysis (PCA), which have successfully been applied to TOF-SIMS imaging data, would also likely be helpful for NFIR data interpretation. In this study, a multicomponent model polymer sample was measured with NFIR and then the image data along with the complex NFIR spectra were analysed by PCA. As a result, the components in the model sample can be separately displayed based on groups of peaks specific to every component indicated by PCA.