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

и другие.

EBioMedicine, Год журнала: 2023, Номер 94, С. 104714 - 104714

Опубликована: Июль 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.

Язык: Английский

Role of Insulin Resistance in MAFLD DOI Open Access

Yoshitaka Sakurai,

Naoto Kubota, Toshimasa Yamauchi

и другие.

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(8), С. 4156 - 4156

Опубликована: Апрель 16, 2021

Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as dysfunction-associated (MAFLD). Metabolic this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and syndrome, with insulin resistance common pathophysiology. Imbalance between energy intake expenditure results various tissues alteration gut microbiota, resulting fat accumulation liver. The role genetics also been revealed hepatic fibrosis. In process liver, intracellular damage well further potentiates inflammation, fibrosis, carcinogenesis. Increased lipogenic substrate supply from other tissues, zonation Irs1, factors, including ER stress, play crucial roles increased de novo lipogenesis MAFLD resistance. Herein, we provide an overview factors contributing systemic local progression MAFLD.

Язык: Английский

Процитировано

274
NAFLD: Mechanisms, Treatments, and Biomarkers DOI Creative Commons
Fatiha Nassir

Biomolecules, Год журнала: 2022, Номер 12(6), С. 824 - 824

Опубликована: Июнь 13, 2022

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated (MAFLD), is one of the most common causes diseases worldwide. NAFLD growing in parallel with obesity epidemic. No pharmacological treatment available to treat NAFLD, specifically. The reason might be that a multi-factorial an incomplete understanding mechanisms involved, absence accurate and inexpensive imaging tools, lack adequate non-invasive biomarkers. consists accumulation excess lipids liver, causing lipotoxicity progress steatohepatitis (NASH), fibrosis, hepatocellular carcinoma. for pathogenesis current interventions management disease, role sirtuins as potential targets are discussed here. In addition, diagnostic non-coding RNAs emerging biomarkers summarized. availability biomarkers, diagnosis tools crucial detection early signs progression NAFLD. This will expedite clinical trials validation therapeutic treatments.

Язык: Английский

Процитировано

250
Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways DOI Creative Commons
Olufunto O. Badmus,

Sarah A. Hillhouse,

Christopher D. Anderson

и другие.

Clinical Science, Год журнала: 2022, Номер 136(18), С. 1347 - 1366

Опубликована: Сен. 1, 2022

Abstract The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the combination with metabolic dysfunction form overweight or obesity and insulin resistance. It also associated an increased cardiovascular risk, including hypertension atherosclerosis. Hepatic lipid metabolism regulated by uptake export acids, de novo lipogenesis, utilization β-oxidation. When balance between these pathways altered, hepatic commences, long-term activation inflammatory fibrotic can progress to worsen disease. This review discusses details molecular mechanisms regulating lipids emerging therapies targeting as potential future treatments for MAFLD.

Язык: Английский

Процитировано

174
A subset of Kupffer cells regulates metabolism through the expression of CD36 DOI
Camille Blériot, Emelie Barreby, Garett Dunsmore

и другие.

Immunity, Год журнала: 2021, Номер 54(9), С. 2101 - 2116.e6

Опубликована: Авг. 31, 2021

Язык: Английский

Процитировано

158
Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease DOI
Soo Lim, Jin‐Wook Kim, Giovanni Targher

и другие.

Trends in Endocrinology and Metabolism, Год журнала: 2021, Номер 32(7), С. 500 - 514

Опубликована: Май 8, 2021

Язык: Английский

Процитировано

151
Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis DOI Creative Commons
Kuei‐Chuan Lee, Pei-Shan Wu, Han‐Chieh Lin

и другие.

Clinical and Molecular Hepatology, Год журнала: 2022, Номер 29(1), С. 77 - 98

Опубликована: Окт. 13, 2022

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. dysfunction lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress would further contribute to hepatocyte injury death, leading inflammation immune in the liver. During healing process, accumulation an excessive amount fibrosis might occur while healing. development NASH liver fibrosis, gut-liver axis, adipose-liver renin-angiotensin system (RAS) may be dysregulated impaired. Translocation bacteria or its end-products entering could activate hepatocytes, Kupffer cells, stellate exacerbating steatosis, inflammation, fibrosis. Bile acids regulate glucose through Farnesoid X receptors intestine. Increased adipose tissue-derived non-esterified fatty aggravate leptin also plays a role fibrogenesis, decreased adiponectin resistance. Moreover, dysregulation peroxisome proliferator-activated liver, adipose, muscle tissues impair metabolism. In addition, RAS acid metabolism, treatment includes lifestyle modification, pharmacological therapy, non-pharmacological therapy. Currently, weight reduction modification surgery most effective However, vitamin E, pioglitazone, obeticholic have been suggested. this review, we will introduce some new clinical trials experimental therapies for related

Язык: Английский

Процитировано

109
Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity DOI Creative Commons
Jinjin Jiang, Guofu Zhang,

Jia-Yi Zheng

и другие.

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Апрель 12, 2022

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, was reported to be capable inhibiting ferroptosis, which is a recognized type regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression NAFLD, experimental evidence limited. Hence, our study aimed investigate high-fat diet (HFD)-induced NAFLD and further elucidate underlying molecular mechanism. Methods: C57BL/6J mice were fed either normal (ND), HFD, or HFD supplemented with for 12 weeks. Hepatic lipid peroxidation, steatosis, iron overload examined. In vitro, steatotic L-02 cells used potential Results: We found that caused accumulation liver, rescued by supplementation. Consistent vivo results, alleviated droplet reduced levels reactive oxygen species (ROS) cells. Using mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) specific inhibitor (Fer-1), we remarkably peroxidation reducing MtROS-mediated Conclusion: Our data showed consumption induced triggered ultimately leading lipotoxicity, can quercetin. Findings from this provide new insight into prevention treatment NAFLD.

Язык: Английский

Процитировано

91
Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathway DOI Open Access

Yue-Qiang Huang,

Yi-Xi Tang,

Bai-Hao Qiu

и другие.

Food and Chemical Toxicology, Год журнала: 2022, Номер 165, С. 113119 - 113119

Опубликована: Май 7, 2022

Язык: Английский

Процитировано

78
Obesity-induced dysregulation of skin-resident PPARγ+ Treg cells promotes IL-17A-mediated psoriatic inflammation DOI Creative Commons
Pulavendran Sivasami, Cody Elkins, Pamela P. Diaz-Saldana

и другие.

Immunity, Год журнала: 2023, Номер 56(8), С. 1844 - 1861.e6

Опубликована: Июль 20, 2023

Язык: Английский

Процитировано

49
The Multifaceted Roles of Macrophages in NAFLD Pathogenesis DOI Creative Commons

Joscha Vonderlin,

Triantafyllos Chavakis, Michael H. Sieweke

и другие.

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2023, Номер 15(6), С. 1311 - 1324

Опубликована: Янв. 1, 2023

Nonalcoholic fatty liver disease (NAFLD) is the manifestation of metabolic syndrome. NAFLD constitutes a spectrum pathologies ranging from simple hepatic steatosis (nonalcoholic liver) to more progressive form steatohepatitis and fibrosis, which can culminate in cirrhosis hepatocellular carcinoma. Macrophages play multiple roles context pathogenesis by regulating inflammatory responses homeostasis thereby may represent an attractive therapeutic target. Advances high-resolution methods have highlighted extraordinary heterogeneity plasticity macrophage populations activation states thereof. Harmful/disease-promoting as well beneficial/restorative phenotypes co-exist are dynamically regulated, thus this complexity must be taken into consideration strategies concerning targeting. Macrophage includes their distinct ontogeny (embryonic Kupffer cells vs bone marrow-/monocyte-derived macrophages) functional phenotype, for example, phagocytes, lipid- scar-associated macrophages, or restorative macrophages. Here, we discuss multifaceted role macrophages steatosis, steatohepatitis, transition fibrosis carcinoma, focusing on both beneficial maladaptive functions at different stages. We also highlight systemic aspect dysregulation illustrate contribution reciprocal crosstalk between organs compartments (eg, gut-liver axis, adipose tissue, cardiohepatic interactions). Furthermore, current state development pharmacologic treatment options targeting biology.

Язык: Английский

Процитировано

46