Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity

Fujikawa, Teppei; Fujita, Ryo; Iwaki, Yoko; Matsumura, Shigenobu; Fushiki, Tohru; Inoue, Kazuo

doi:10.1016/j.physbeh.2010.06.006

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Since TGF-β3 increased noradrenaline levels in the paraventricular and ventromedial hypothalamic nuclei and chemical lesion of noradrenaline input to these nuclei completely abolished the regulatory effect of TGF-β on fat oxidation it has been suggested that TGF-β in the brain enhances fat oxidation via noradrenergic neurons in the paraventricular and ventromedial hypothalamic nuclei ). An inhibitor of FA oxidation could induce an activation of TGF-β in the CSF suggesting that shortage of energy derived from fatty acids leads to the activation of TGF-β (Fujikawa et al, 2011).…”

Section: Involvement In Inflammatory and Neuroendocrine Functionsmentioning

confidence: 99%

Transforming Growth Factor Beta in the Central Nervous System

Dobolyi¹

2012

Neuroscience - Dealing With Frontiers

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Section: Involvement In Inflammatory and Neuroendocrine Functionsmentioning

confidence: 99%

Transforming Growth Factor Beta in the Central Nervous System

Dobolyi¹

2012

Neuroscience - Dealing With Frontiers

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“…TGF-b is known to mediate tissue inflammation and damage accompanied by tissue fibrosis, and it also plays an essential role in activating CFs. TGF-b causes fibroblast activation, proliferation, and differentiation into myofibroblasts which secreting ECM proteins [11,12]. A typical pathway for TGF-b1 signaling involves phosphorylation of SMAD family member (Smad) 2/3, which subsequently binds to Smad4 and causes nuclear translocation.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Zheng¹,

Zhang²,

Hu³

et al. 2019

The FEBS Journal

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Diabetic cardiomyopathy (DCM)—ventricular dysfunction in the absence of underlying heart disease—is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure. Although it is well‐established that the transforming growth factor‐beta signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene reg;ulation of key signaling effectors in DCM‐associated cardiac fibrosis. A recently emerged hotspot in the field of gene regulation is the role of long noncoding RNAs (lncRNAs). Recent evidence indicates that lncRNAs play a critical role in cardiac fibrosis; however, in DCM, the function of these regulatory RNAs have not been studied in depth. In this study, we identified a conserved cardiac‐specific lncRNA named colorectal neoplasia differentially expressed (Crnde). By analyzing 376 human heart tissues, it was found that Crnde expression is negatively correlated with that of cardiac fibrosis marker genes. Moreover, Crnde expression was shown to be enriched in cardiac fibroblasts (CFs). Overexpression of Crnde attenuated cardiac fibrosis and enhanced cardiac function in mice with DCM. Further, in vitro experiments showed that Crnde negatively regulates the myofibroblast differentiation of CFs. The expression of Crnde was activated by SMAD family member 3 (Smad3), shedding light on the underlying molecular mechanism. Interestingly, Crnde also inhibited the transcriptional activation of Smad3 on target genes, thereby inhibiting the expression of myofibroblastic marker genes in CFs. Overall, our data provide valuable insights into the development of potential anti‐cardiac fibrosis strategies centered on lncRNAs, for the treatment of DCM.

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“…In addition, noradrenergic projections to the hypothalamus, which plays a pivotal role in the regulation of energy metabolism, were activated by intracisternal administration of TGF-␤ (19), and inhibition of fatty acid oxidation by i.p. administration of mercaptoacetate led to an increase in active TGF-␤ in rat CSF (20). From these data, TGF-␤ in the brain seemed to be closely linked to the energy metabolism state in the body and to play an important role in the regulation of energy metabolism.…”

Section: Discussionmentioning

confidence: 81%

Blood Lactate Functions as a Signal for Enhancing Fatty Acid Metabolism during Exercise via TGF-^|^beta; in the Brain

Yamada

Iwaki

Kitaoka

et al. 2012

J Nutr Sci Vitaminol

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Summary Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-␤ (TGF-␤ ) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-␤ . Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-␤ in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-␤ to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-␤ in the brain. Key Words lactate, TGF-␤ , exercise, respiratory gas analysis, spontaneous motor activity Recently, lactate has been recognized as a good energy source for the central nervous system. Wyss et al.( 1 ) demonstrated that lactate instead of glucose could maintain neuronal activities, and that when both substrates are available, the brain preferentially utilizes lactate. The study, however, implies that lactate is not a direct cause of feelings of fatigue by acting on the brain, and negated the classical view of lactate as a fatigue substance. Blood lactate increases during physical exercise, with skeletal muscles being the major sites of lactate production [see Bergersen ( 2 ) for review]. Increased lactate concentration serves as a signal indicating an increase in the relative ratio of glycolytic energy production, and this signal may function to induce changes in whole-body energy metabolism. Lactate directly acts on neurons and affects their activities. The activities of some neurons in the ventromedial hypothalamus are affected by glucose, whereas some neurons show increased firing rate upon lactate administration ( 3 ). Patil and Briski ( 4 , 5 ) reported the activation of catecholaminergic neurons in the hindbrain by blocking the supply of lactate into the brain with ␣ -cyano-4-hydroxycinnamic acid. These findings indicate that lactate functions as an index for monitoring the energy metabolism status of peripheral organs.We developed a model (Sim-Ex) that simulates physical exercise by inducing skeletal muscle contraction through electrical stimulation in the hindlimbs of anesthetized rats ( 6 ). Sim-Ex with a frequency of 2 Hz could reproduce an exercise load that corresponded to lowintensity exercise. We reported significant increases in the concentrations of blood lactate and active transforming growth factor-␤ (TGF-␤ ) in cerebrospinal fluid (CSF) 5 and 10 min after the onset of Sim-Ex, respectively ( 7 ). A fraction of active TGF-␤ increased in rat CSF after exhaustion by exercise ( 8 ). ...

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Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity

Cited by 8 publications

References 43 publications

Transforming Growth Factor Beta in the Central Nervous System

Transforming Growth Factor Beta in the Central Nervous System

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Blood Lactate Functions as a Signal for Enhancing Fatty Acid Metabolism during Exercise via TGF-^|^beta; in the Brain

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