Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice

2018 ◽  
Vol 66 (6) ◽  
pp. 1533-1542 ◽  
Author(s):  
Wenping Xie ◽  
Wenpeng Zhang ◽  
Juan Ren ◽  
Wentao Li ◽  
Lili Zhou ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Tricarboxylic Acid Cycle ◽  
Acid Synthesis ◽  
Tricarboxylic Acid ◽  
Male Mice ◽  
Acid Cycle ◽  
Metabolic Alterations

scholarly journals Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia trachomatis during Treatment with β-Lactam Antimicrobials

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Kensuke Shima ◽  
Inga Kaufhold ◽  
Thomas Eder ◽  
Nadja Käding ◽  
Nis Schmidt ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chlamydia Trachomatis ◽  
Fatty Acid Synthesis ◽  
Tricarboxylic Acid Cycle ◽  
Acid Synthesis ◽  
Tricarboxylic Acid ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Content Type ◽  
Acid Cycle

ABSTRACT Infection with the obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in C. trachomatis infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness. Here, we report the mechanism for C. trachomatis regulating host signaling processes and mitochondrial function, which can be used for chlamydial metabolic reprogramming during treatment with β-lactam antimicrobials. Activation of signal transducer and activator of transcription 3 (STAT3) is a well-known host response in various bacterial and viral infections. In C. trachomatis infection, inactivation of STAT3 by host protein tyrosine phosphatases increased mitochondrial respiration in both the absence and presence of β-lactam antimicrobials. However, during treatment with β-lactam antimicrobials, C. trachomatis increased the production of citrate as well as the activity of host ATP-citrate lyase involved in fatty acid synthesis. Concomitantly, chlamydial metabolism switched from the tricarboxylic acid cycle to fatty acid synthesis. This metabolic switch was a unique response in treatment with β-lactam antimicrobials and was not observed in gamma interferon (IFN-γ)-induced persistent infection. Inhibition of fatty acid synthesis was able to attenuate β-lactam-induced chlamydial persistence. Our findings highlight the importance of the mitochondrion-fatty acid interplay for the metabolic reprogramming of C. trachomatis during treatment with β-lactam antimicrobials. IMPORTANCE The mitochondrion generates most of the ATP in eukaryotic cells, and its activity is used for controlling the intracellular growth of Chlamydia trachomatis. Furthermore, mitochondrial activity is tightly connected to host fatty acid synthesis that is indispensable for chlamydial membrane biogenesis. Phospholipids, which are composed of fatty acids, are the central components of the bacterial membrane and play a crucial role in the protection against antimicrobials. Chlamydial persistence that is induced by various stimuli is clinically relevant. While one of the well-recognized inducers, β-lactam antimicrobials, has been used to characterize chlamydial persistence, little is known about the role of mitochondria in persistent infection. Here, we demonstrate how C. trachomatis undergoes metabolic reprogramming to switch from the tricarboxylic acid cycle to fatty acid synthesis with promoted host mitochondrial activity in response to treatment with β-lactam antimicrobials.

scholarly journals Detection of myocardial medium‐chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1– 13 C]octanoate

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Hikari A.I. Yoshihara ◽  
Jessica A.M. Bastiaansen ◽  
Magnus Karlsson ◽  
Mathilde H. Lerche ◽  
Arnaud Comment ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Chain Fatty Acid ◽  
Medium Chain Fatty Acid ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Medium Chain

scholarly journals The Involvement of PPARs in the Peculiar Energetic Metabolism of Tumor Cells

2018 ◽  
Author(s):  
Andrea Antonosante ◽  
Michele d'Angelo ◽  
Vanessa Castelli ◽  
Mariano Catanesi ◽  
Dalila Iannotta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Cancer Metabolism ◽  
Cholesterol Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Energetic Metabolism ◽  
Metabolic Alterations ◽  
Long Time

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

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