Blunted Expression of PPARa in Mice with FABP-4 and -5 Deficiency under Acute Cold Exposure

Brown Adipose Tissue (BAT) is a nonshivering thermogenesis organ during cold exposure. Peroxisomal proliferator activated receptor alpha (PPARa) is the member of the nuclear hormone receptor superfamily and primarily expressed in BAT and liver. PPARa is coordinated with uncoupling protein 1 (UCP1) to regulate fatty acid metabolism in BAT. Fatty acid binding protein (FABP)-4 and-5 play role in adaptive response under fasting and cold exposure. The purpose of this study was to investigate the expression of PPARa in mice with FABP4/5 deficiency (DKO). Wildtype (WT) and DKO mice were exposed to cold for 2 hours under fed or 20 hours-fasted conditions. BAT was collected and further mRNA level of PPARa was examined using quantitative real-time PCR. As the result, PPARa gene expression in WT mice were increased 50% and 100% in fed and fasted condition respectively after cold exposure. There was no alteration in PPARa expression in  BAT of DKO mice. As conclusion, The functional FABP-4 and -5 are necessary to modulate PPARa gene expression in Brown Adipose Tissue under acute cold exposure  Keywords: Acute cold exposure; FABP4; FABP5; Fasting  PPAR

Learning to Select, Track, and Generate for Data-to-Text

We propose a data-to-text generation model with two modules, one for tracking and the other for text generation. Our tracking module selects and keeps track of salient information and memorizes which record has been mentioned. Our generation module generates a summary conditioned on the state of tracking module. Our model is considered to simulate the human-like writing process that gradually selects the information by determining the intermediate variables while writing the summary. In addition, we also explore the effectiveness of the writer information for generation. Experimental results show that our model outperforms existing models in all evaluation metrics even without writer information. Incorporating writer information further improves the performance, contributing to content planning and surface realization.Comment: ACL 201

The Upregulation of <i>Carnitine Palmitoyltransferase 1a</i> (<i>CPT1a</i>) Expression under Prolonged Fasting in CD36 Knockout Mice

Food deprivation is one of the extreme conditions that mammals have to survive. The majority of the tissues, excluding the brain and red blood cells, depend on the fatty acids (FA) utilization to produce energy. We recently showed in mice lacking for CD36 (CD36−/−), the uptake of FA is limited with dramatically increased of glucose uptake in heart and skeletal muscle in fasted condition, indicating a compensatory mechanism of organ to fulfill an energy demand. The liver is the central tissue maintaining metabolic homeostasis in fasted state. Synthesize adenosine triphosphate (ATP) in the mitochondria via beta-oxidation was mediated by carnitine palmitoyltransferase 1a (CPT1a). The objective of this research was to explore the role of CD36 in CPT1a expression in the fasted state. This research was conducted at Gunma University Japan in 2015. The method was in vivo-experimental, that we used CD36−/− and wild-type (WT) mice, as a control. The gene expression of CPT1a was measured by real-time PCR. Fasting condition up regulated mRNA expression of CPT1a in both WT and CD36−/− mice in 24 h and 48 h. However in CD36−/− mice, the mRNA expression of CPT1a in 24 h fasted state was lower very significantly than WT mice (p<0.01). We demonstrate that CD36 deficiency up regulate CPT1a gene expression, suggested that CD36 is essential for nutrient homeostasis when requirement for FA is increased and obtainability of nutrient is inadequate.   PENINGAKTAN EKSPRESI GEN CARNITINE PALMITOYLTRANSFERASE 1A (CPT1A) PADA CD36 KNOCKOUT MICE DALAM KEADAAN PUASA Kekurangan makanan adalah salah satu kondisi ekstrem yang harus dihindari oleh mamalia. Sebagian besar jaringan, kecuali otak dan sel darah merah sangat bergantung pada pemanfaatan langsung asam lemak untuk menghasilkan energi. Penelitian kami sebelumnya menunjukkan pada mencit dengan defisiensi CD36 (CD36−/−), serapan asam lemak terbatas karena peningkatan pengambilan glukosa hati dan otot rangka secara signifikan dalam kondisi puasa yang mengindikasikan mekanisme kompensasi organ untuk memenuhi kebutuhan energi. Hati adalah jaringan sentral yang menjaga homeostasis metabolik tubuh dalam keadaan berpuasa. Sintesis adenosine triphosphate (ATP) di mitokondria melalui beta-oksidasi dimediasi oleh carnitine palmitoyltransferase 1a (CPT1a). Tujuan penelitian ini mengetahui peran CD36 dalam ekspresi CPT1a dalam keadaan puasa. Penelitian ini dilakukan di Universitas Gunma Jepang pada tahun 2015. Metode penelitian ini adalah eksperimental in vivo dengan menggunakan mencit CD36−/− dan wild type (WT) sebagai kontrol. Ekspresi gen CPT1a diukur dengan real-time PCR. Puasa meningkatkan ekspresi mRNA CPT1a pada mencit WT dan CD36−/− baik setelah puasa selama 24 jam dan 48 jam. Namun, pada mencit CD36−/−, ekspresi mRNA CPT1a dalam keadaan setelah dipuasakan 24 jam lebih rendah daripada mencit WT (p<0,01). Penelitian ini menunjukkan bahwa defisiensi CD36 mengatur ekspresi gen CPT1a sehingga CD36 sangat diperlukan untuk homeostasis nutrisi ketika kebutuhan asam lemak meningkat dan kemungkinan ketersediaan nutrisi terbatas

A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis

Stearoyl-CoA Desaturase-1 (SCD1) Augments Saturated Fatty Acid-Induced Lipid Accumulation and Inhibits Apoptosis in Cardiac Myocytes

Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS) generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis

Cardiac Metabolism and Contractile Function in Mice with Reduced Trans-Endothelial Fatty Acid Transport

The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps&mdash;the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins. In the heart, impaired trans-endothelial FA (TEFA) transport causes reduced FA uptake, with a compensatory increase in glucose use. In most cases, mice with reduced FA uptake exhibit preserved cardiac function under unstressed conditions. When the workload is increased, however, the total energy supply relative to its demand (estimated with pool size in the tricarboxylic acid (TCA) cycle) is significantly diminished, resulting in contractile dysfunction. The supplementation of alternative fuels, such as medium-chain FAs and ketone bodies, at least partially restores contractile dysfunction, indicating that energy insufficiency due to reduced FA supply is the predominant cause of cardiac dysfunction. Based on recent in vivo findings, this review provides the following information related to TEFA transport: (1) the mechanisms of FA uptake by the heart, including TEFA transport; (2) the molecular mechanisms underlying the induction of genes associated with TEFA transport; (3) in vivo cardiac metabolism and contractile function in mice with reduced TEFA transport under unstressed conditions; and (4) in vivo contractile dysfunction in mice with reduced TEFA transport under diseased conditions, including an increased afterload and streptozotocin-induced diabetes

Cardiac Metabolism and Contractile Function in Mice with Reduced Trans-Endothelial Fatty Acid Transport

The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps—the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins. In the heart, impaired trans-endothelial FA (TEFA) transport causes reduced FA uptake, with a compensatory increase in glucose use. In most cases, mice with reduced FA uptake exhibit preserved cardiac function under unstressed conditions. When the workload is increased, however, the total energy supply relative to its demand (estimated with pool size in the tricarboxylic acid (TCA) cycle) is significantly diminished, resulting in contractile dysfunction. The supplementation of alternative fuels, such as medium-chain FAs and ketone bodies, at least partially restores contractile dysfunction, indicating that energy insufficiency due to reduced FA supply is the predominant cause of cardiac dysfunction. Based on recent in vivo findings, this review provides the following information related to TEFA transport: (1) the mechanisms of FA uptake by the heart, including TEFA transport; (2) the molecular mechanisms underlying the induction of genes associated with TEFA transport; (3) in vivo cardiac metabolism and contractile function in mice with reduced TEFA transport under unstressed conditions; and (4) in vivo contractile dysfunction in mice with reduced TEFA transport under diseased conditions, including an increased afterload and streptozotocin-induced diabetes