Mammals possess an intricate regulatory system for controlling flux through fuel utilization pathways in response to the dietary availability of particular macronutrients. Under fasting conditions, for instance, mammals initiate a whole body metabolic response that limits glucose utilization and favors fatty acid oxidation. Understanding the underlying mechanisms by which this process occurs will facilitate the development of new treatments for metabolic disorders such as type II diabetes and obesity. One of the recently identified components of the signal transduction pathway involved in metabolic reprogramming is PGC-1alpha. This transcriptional coactivator is able to coordinate the expression of a wide array of genes involved in glucose and fatty acid metabolism. The nutrient-mediated control of PGC-1alpha activity is tightly correlated with its acetylation state. In this review, we evaluate how the nutrient regulation of PGC-1alpha activity squares with the regulation of its acetylation state by the deacetylase Sirt1 and the acetyltransferase GCN5. We also propose an outline of additional experimental directives that will help to shed additional light on this very powerful transcriptional coactivator.
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http://dx.doi.org/10.1016/j.bbapap.2009.11.023 | DOI Listing |
PLoS One
January 2025
Department of Biological Sciences, Purdue University Fort Wayne, Fort Wayne, Indiana, United States of America.
Present study aimed at improving the immune and antioxidant response of Pacific white shrimp (Litopenaeus vannamei) cultured at high stocking density fed with 0.2% supplementation of lauric acid (LA) and N-acetyl-L-cysteine (NAC). Shrimp (initial average weight = 0.
View Article and Find Full Text PDFNat Metab
January 2025
Department of Bioengineering, University of California, University of California, San Diego, La Jolla, CA, USA.
The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.
View Article and Find Full Text PDFBioresour Technol
January 2025
Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China; Department of Chemical Engineering, Tsinghua University, Beijing, China; Key Lab for Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China; School of Chemistry and Chemical Engineering/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University, Shihezi, Xinjiang, China. Electronic address:
Pinene is a plant volatile monoterpenoid which is used in the fragrance, pesticide, and biofuel industries. Although α-pinene has been synthesized in microbial cell factories, the low synthesis efficiency has thus far limited its production. In this study, the cell growth and α-pinene production of the engineered yeast were decoupled by a dynamic regulation strategy, resulting in a 101.
View Article and Find Full Text PDFDev Cell
January 2025
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China. Electronic address:
Cleavage-stage arrest in human embryos substantially limits the success rate of infertility treatment, with maternal-to-zygotic transition (MZT) abnormalities being a potential contributor. However, the underlying mechanisms and regulators remain unclear. Here, by performing allelic transcriptome analysis on human preimplantation embryos, we accurately quantified MZT progression by allelic ratio and identified a fraction of 8-cell embryos, at the appropriate developmental time point and exhibiting normal morphology, were in transcriptionally arrested status.
View Article and Find Full Text PDFJ Nat Prod
January 2025
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
(-)-Cryptanoside A () was identified previously as a major cytotoxic component of the stems of collected in Laos, which mediates its activity by targeting Na/K-ATPase (NKA), with hydrogen bonds formed between its 11- and 4'-hydroxy groups and NKA being observed in its docking profile. In a continuing investigation, and its 17-epimer, (-)-17--cryptanoside A (), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid () and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone () pregnane-type steroids were isolated from . In addition, (-)-11,4'-di--acetylcryptanoside A () has been synthesized from the acetylation of .
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