Alterations of hepatic energy metabolism in murine models of obesity, diabetes and fatty liver diseases DOI Creative Commons
Bedair Dewidar, Lucia Mastrototaro, Cornelia Englisch

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104714 - 104714

Published: July 16, 2023

Disturbed hepatic energy metabolism contributes to non-alcoholic fatty liver (NAFLD), but the development of changes over time and obesity- or diabetes-related mechanisms remained unclear.Two-day old male C57BL/6j mice received streptozotocin (STZ) placebo (PLC) then high-fat (HFD) regular chow diet (RCD) from week 4 (W4) either W8 W16, yielding control [CTRL = PLC + RCD], diabetes [DIAB STZ obesity [OBES HFD] steatohepatitis [NASH models. Mitochondrial respiration was measured by high-resolution respirometry insulin-sensitive glucose hyperinsulinemic-euglycemic clamps with stable isotope dilution.NASH showed higher steatosis NAFLD activity already at fibrosis W16 (all p < 0.01 vs CTRL). Ballooning increased in DIAB NASH (p At insulin sensitivity 47%, 58% 75% lower DIAB, OBES 0.001 Hepatic uncoupled acid oxidation (FAO)-associated reduced W8, doubled CTRL) correlated biomarkers unfolded protein response (UPR), oxidative stress expression certain enzymes (acetyl-CoA carboxylase 2, Acc2; carnitine palmitoyltransferase I, Cpt1a). Tricarboxylic cycle (TCA)-driven 0.0001 CTRL), which positively genes related lipolysis.Hepatic mitochondria adapt various metabolic challenges increasing FAO-driven respiration, is linked dysfunctional UPR, systemic stress, resistance altered lipid metabolism. In a model, TCA-linked reflected mitochondrial adaptation greater turnover.Funding bodies that contributed this study were listed acknowledgements section.

Language: Английский

Exosomes-regulated lipid metabolism in tumorigenesis and cancer progression DOI

Leiguang Ye,

Yingpu Li, Sifan Zhang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2023, Volume and Issue: 73, P. 27 - 39

Published: May 24, 2023

Language: Английский

Citations

31
CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease DOI
Jan F. C. Glatz, Lisa C. Heather, Joost J.F.P. Luiken

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 104(2), P. 727 - 764

Published: Oct. 26, 2023

The multifunctional membrane glycoprotein CD36 is expressed in different types of cells and plays a key regulatory role cellular lipid metabolism, especially cardiac muscle. facilitates the uptake long-chain fatty acids, mediates signaling, regulates storage oxidation lipids various tissues with active metabolism. deficiency leads to marked impairments peripheral which consequently impact on utilization multiple fuels because integrated nature functional presence at plasma regulated by its reversible subcellular recycling from endosomes under control mechanical, hormonal, nutritional factors. Aberrations this dynamic are causally associated metabolic diseases, particular insulin resistance, diabetic cardiomyopathy, hypertrophy. Recent research muscle has disclosed endosomal proton pump vacuolar-type H

Language: Английский

Citations

30
Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis DOI Creative Commons
Shibin Ding,

Xiaolei Chu,

Yuxuan Jin

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 21, 2023

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced that highly related to metabolic disorders and induced by high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as protective bioactive polyphenol in green tea the ability protect against non-alcoholic disease, but molecular mechanism remains poorly deciphered. Ferroptosis plays vital role progression of experimental evidence ferroptosis inhibition limited. Hence, our study aimed investigate effect mechanisms on hepatic mitigate injury diet-fed mice. Methods: Fifty male C57BL/6 mice were fed either standard chow (SCD), diet, or administered ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, steatosis, oxidative stress, iron overload, marker proteins examined. In vitro , steatotic L-02 cells used explore underlying mechanism. Results: research, we found notably alleviated decreased overload inhibited diet-induced murine model disease. experiments, using mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), remarkably stress reducing level cells. Conclusion: Taken together, results revealed may exert effects lipotoxicity inhibiting species-mediated ferroptosis. Findings from provide new insight into prevention treatment strategies pathological processes.

Language: Английский

Citations

28
Nonalcoholic fatty liver disease: Current therapies and future perspectives in drug delivery DOI
Inês Domingues, Isabelle Leclercq, Ana Beloqui

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 363, P. 415 - 434

Published: Oct. 1, 2023

Language: Английский

Citations

28
Alterations of hepatic energy metabolism in murine models of obesity, diabetes and fatty liver diseases DOI Creative Commons
Bedair Dewidar, Lucia Mastrototaro, Cornelia Englisch

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104714 - 104714

Published: July 16, 2023

Disturbed hepatic energy metabolism contributes to non-alcoholic fatty liver (NAFLD), but the development of changes over time and obesity- or diabetes-related mechanisms remained unclear.Two-day old male C57BL/6j mice received streptozotocin (STZ) placebo (PLC) then high-fat (HFD) regular chow diet (RCD) from week 4 (W4) either W8 W16, yielding control [CTRL = PLC + RCD], diabetes [DIAB STZ obesity [OBES HFD] steatohepatitis [NASH models. Mitochondrial respiration was measured by high-resolution respirometry insulin-sensitive glucose hyperinsulinemic-euglycemic clamps with stable isotope dilution.NASH showed higher steatosis NAFLD activity already at fibrosis W16 (all p < 0.01 vs CTRL). Ballooning increased in DIAB NASH (p At insulin sensitivity 47%, 58% 75% lower DIAB, OBES 0.001 Hepatic uncoupled acid oxidation (FAO)-associated reduced W8, doubled CTRL) correlated biomarkers unfolded protein response (UPR), oxidative stress expression certain enzymes (acetyl-CoA carboxylase 2, Acc2; carnitine palmitoyltransferase I, Cpt1a). Tricarboxylic cycle (TCA)-driven 0.0001 CTRL), which positively genes related lipolysis.Hepatic mitochondria adapt various metabolic challenges increasing FAO-driven respiration, is linked dysfunctional UPR, systemic stress, resistance altered lipid metabolism. In a model, TCA-linked reflected mitochondrial adaptation greater turnover.Funding bodies that contributed this study were listed acknowledgements section.

Language: Английский

Citations

26