김경섭 교수

Leptin, the product of the ob gene, controls food-intake and weight loss in the ob mouse. Although the target(s) of the circulating leptin is presumed to be the brain which then orchestrates food-intake and weight loss, how leptin functions in the process of weight loss is unknown. In this report, we present evidence that ob gene expression in cultured cells suppresses acetyl-CoA carboxylase gene expression and lipid synthesis which are induced by hormone treatment. This is the first example in

Expression of the HER2 oncogene is increased in approximately 30% of human breast carcinomas and is closely correlated with the expression of fatty acid synthase (FASN). In the present study, we determined the mechanism by which FASN and acetyl-CoA carboxylase alpha (ACCalpha) could be induced by HER2 overexpression. SK-BR-3 and BT-474 cells, breast cancer cells that overexpress HER2, expressed higher levels of FASN and ACCalpha compared with MCF-7 and MDA-MB-231 breast cancer cells in which HER

Krüppel-like factor 4 (KLF4) is a transcription factor that plays an important role in cell differentiation, proliferation, and survival, especially in the context of cancers. This study revealed that KLF4 activates glycolytic metabolism in breast cancer cells by up-regulating the platelet isoform of phosphofructokinase (PFKP). KLF4 activated the transcription of the PFKP gene by directly binding to the PFKP promoter. Whereas glucose uptake and lactate production were inhibited by the knockdown

Lipin1 expression was induced at a late stage of differentiation of 3T3-L1 preadipocytes and maintained at high levels in mature adipocytes. Knockdown of expression of lipin1 by small interfering RNA in 3T3-L1 preadipocytes almost completely inhibited differentiation into adipocytes, whereas overexpression of lipin1 accelerated adipocyte differentiation, demonstrating that lipin1 is required for adipocyte differentiation. In mature adipocytes, transfection of lipin1-small interfering RNA decreas

Acetyl-CoA carboxylase (ACC) exists as two major isoforms originated from separate genes: ACCalpha (or ACC1) and ACCbeta (or ACC2). Previous data revealed that ACCbeta has two forms of mRNA with different 5'-untranslated regions derived by different usage of promoters, I and II, in human. In this study, we revealed that ACCbeta expression in liver is markedly stimulated by food intake at the transcriptional level. In the process of this induction in rat liver, promoter II plays the major role in

ATP citrate-lyase (ACL) is a key enzyme supplying acetyl-CoA for fatty acid and cholesterol synthesis. Its expression is drastically up-regulated when an animal is fed a low fat, high carbohydrate diet after prolonged fasting. In this report, we describe the role of sterol regulatory element-binding proteins (SREBPs) in the transactivation of the rat ACL promoter. ACL promoter activity was markedly stimulated by the overexpression of SREBP-1a and, to a lesser extent, by SREBP-2 in Alexander huma

Phosphoglucomutase (PGM)1 catalyzes the reversible conversion reaction between glucose-1-phosphate (G-1-P) and glucose-6-phosphate (G-6-P). Although both G-1-P and G-6-P are important intermediates for glucose and glycogen metabolism, the biological roles and regulatory mechanisms of PGM1 are largely unknown. In this study we found that T553 is obligatory for PGM1 stability and the last C-terminal residue, T562, is critical for its activity. Interestingly, depletion of PGM1 was associated with d

Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial f

Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator

Background and Purpose The blood supply to the medulla oblongata is distinct from that of other areas of the brainstem, and thus the mechanism underlying medullary infarctions may be distinct. However, few studies have investigated this. Methods Of 3833 stroke patients who were on the stroke registry between February 1999and April 2008, those with medullary infarctions demonstrated on diffusion-weighted magnetic resonance imaging were enrolled. We analyzed the topography, the involved arterial t

Acetyl-CoA carboxylase beta (ACCbeta) is a critical enzyme in the regulation of fatty acid oxidation and is dominantly expressed in the skeletal muscle, heart, and liver. It has been established that two promoters, P-I and P-II, control the transcription of the ACCbeta gene. However, the precise mechanism involved in controlling tissue-specific gene expression of ACCbeta is largely unknown yet. In this study we revealed that promoter P-I, active in the skeletal muscle and heart but not in the li