The fate of pyruvate dictates cell growth by modulating cellular redox potential DOI Open Access
Ashish G. Toshniwal,

Geanette Lam,

Alex J. Bott

и другие.

Опубликована: Дек. 30, 2024

Pyruvate occupies a central node in carbohydrate metabolism such that how it is produced and consumed can optimize cell for energy production or biosynthetic capacity. This has been primarily studied proliferating cells, but observations from the post-mitotic Drosophila fat body led us to hypothesize pyruvate fate might dictate rapid growth observed this organ during development. Indeed, we demonstrate augmented mitochondrial import prevented cells vivo as well cultured mammalian hepatocytes human hepatocyte-derived vitro . effect on size was caused by an increase NADH/NAD + ratio, which rewired toward gluconeogenesis suppressed biomass-supporting glycolytic pathway. Amino acid synthesis decreased, resulting loss of protein growth. Surprisingly, all occurred face activated pro-growth signaling pathways, including mTORC1, Myc, PI3K/Akt. These highlight evolutionarily conserved role setting balance between extraction biomass specialized cells.

Язык: Английский

Regular exercise alleviates metabolic dysfunction-associated steatohepatitis through rescuing mitochondrial oxidative stress and dysfunction in liver DOI
Baoxuan Lin, Tong Wu, Mohammad Nasb

и другие.

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
Function of PNPLA3 I148M—Lessons From In Vivo Studies in Humans DOI Open Access
Hannele Yki‐Järvinen, Panu K. Luukkonen

Liver International, Год журнала: 2025, Номер 45(4)

Опубликована: Март 7, 2025

Steatotic liver disease (SLD) associated with insulin resistance (IR) and the metabolic syndrome ('IR-SLD') increases risk of disease, type 2 diabetes cardiovascular (CVD). SLD PNPLA3 I148M variant ('PNPLA3-SLD') also predisposes individuals to but protects against CVD. Although in real life two causes commonly co-exist, opposite effects 'IR-SLD' 'PNPLA3-SLD' on CVD suggest their pathogenesis differs. This review summarises human data comparing lipidome, hepatic handling fatty acids, pathways intrahepatocellular triglyceride synthesis, circulating lipids lipoproteins adipose tissue inflammation. We discuss how steatosis carriers leads defects mitochondrial function.

Язык: Английский

Процитировано

0
Integrated transcriptomics and metabolomics to explore the varied hepatic toxicity induced by aged- and pristine-microplastics: in vivo and human-originated liver organoids-based in vitro study DOI
Wei Cheng,

Yifei You,

Hange Chen

и другие.

Environmental Research, Год журнала: 2025, Номер unknown, С. 121820 - 121820

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway DOI
Rong Liu, Yu Zhang, Min Liu

и другие.

The Journal of Nutritional Biochemistry, Год журнала: 2024, Номер unknown, С. 109808 - 109808

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

1
The fate of pyruvate dictates cell growth by modulating cellular redox potential DOI Open Access
Ashish G. Toshniwal,

Geanette Lam,

Alex J. Bott

и другие.

Опубликована: Дек. 30, 2024

Pyruvate occupies a central node in carbohydrate metabolism such that how it is produced and consumed can optimize cell for energy production or biosynthetic capacity. This has been primarily studied proliferating cells, but observations from the post-mitotic Drosophila fat body led us to hypothesize pyruvate fate might dictate rapid growth observed this organ during development. Indeed, we demonstrate augmented mitochondrial import prevented cells vivo as well cultured mammalian hepatocytes human hepatocyte-derived vitro . effect on size was caused by an increase NADH/NAD + ratio, which rewired toward gluconeogenesis suppressed biomass-supporting glycolytic pathway. Amino acid synthesis decreased, resulting loss of protein growth. Surprisingly, all occurred face activated pro-growth signaling pathways, including mTORC1, Myc, PI3K/Akt. These highlight evolutionarily conserved role setting balance between extraction biomass specialized cells.

Язык: Английский

Процитировано

1
Nature and Nurture in Familial Aggregation of Steatotic Liver Disease DOI Open Access

Juho Asteljoki,

Panu K. Luukkonen

Clinical Gastroenterology and Hepatology, Год журнала: 2024, Номер 22(11), С. 2197 - 2198

Опубликована: Апрель 6, 2024

Язык: Английский

Процитировано

0
Novel HSD17B13 Inhibitors for Treating Liver Diseases DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(6), С. 771 - 772

Опубликована: Май 16, 2024

Provided herein are novel HSD17B13 inhibitors, pharmaceutical compositions, use of such compounds in treating liver diseases, and processes for preparing compounds.

Язык: Английский

Процитировано

0
The fate of pyruvate dictates cell growth by modulating cellular redox potential DOI Creative Commons
Ashish G. Toshniwal,

Geanette Lam,

Alex J. Bott

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 24, 2024

Pyruvate occupies a central node in carbohydrate metabolism such that how it is produced and consumed can optimize cell for energy production or biosynthetic capacity. This has been primarily studied proliferating cells, but observations from the post-mitotic

Язык: Английский

Процитировано

0
Reduced Liver Mitochondrial Energy Metabolism Impairs Food Intake Regulation Following Gastric Preloads and Fasting DOI Creative Commons

Michael E. Ponte,

John C. Prom,

Mallory A. Newcomb

и другие.

Опубликована: Окт. 29, 2024

Summary The capacity of the liver to serve as a peripheral sensor in regulation food intake has been debated for over half century. anatomical position and physiological roles suggest it is prime candidate an interoceptive tissue systemic energy state. Importantly, maintenance ATP levels within- meal inhibition impaired human subjects with obesity obese pre- clinical models. We demonstrate that decreased hepatic mitochondrial metabolism liver-specific, heterozygous PGC1a mice results reduced response changes ΔGATP following fasting. These impairments state are associated larger longer meals during chow feeding, dose-dependent mixed individual nutrient oral pre-loads, greater acute fasting-induced intake. data support previous work proposing liver-mediated through modulation satiation signals.

Язык: Английский

Процитировано

0
The fate of pyruvate dictates cell growth by modulating cellular redox potential DOI Open Access
Ashish G. Toshniwal,

Geanette Lam,

Alex J. Bott

и другие.

Опубликована: Дек. 30, 2024

Pyruvate occupies a central node in carbohydrate metabolism such that how it is produced and consumed can optimize cell for energy production or biosynthetic capacity. This has been primarily studied proliferating cells, but observations from the post-mitotic Drosophila fat body led us to hypothesize pyruvate fate might dictate rapid growth observed this organ during development. Indeed, we demonstrate augmented mitochondrial import prevented cells vivo as well cultured mammalian hepatocytes human hepatocyte-derived vitro . effect on size was caused by an increase NADH/NAD + ratio, which rewired toward gluconeogenesis suppressed biomass-supporting glycolytic pathway. Amino acid synthesis decreased, resulting loss of protein growth. Surprisingly, all occurred face activated pro-growth signaling pathways, including mTORC1, Myc, PI3K/Akt. These highlight evolutionarily conserved role setting balance between extraction biomass specialized cells.

Язык: Английский

Процитировано

0