miR-301a Deficiency Attenuates the Macrophage Migration and Phagocytosis through YY1/CXCR4 Pathway DOI Creative Commons
Jiawei Xu,

Lanya Fu,

Junyao Deng

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(24), P. 3952 - 3952

Published: Dec. 7, 2022

(1) Background: the miR-301a is well known involving proliferation and migration of tumor cells. However, role in phagocytosis macrophages still unclear. (2) Methods: sciatic nerve injury, liver injury models, as primary macrophage cultures were prepared from knockout (KO) wild type (WT) mice to assess macrophage’s capabilities. Targetscan database analysis, Western blotting, siRNA transfection, CXCR4 inhibition or activation performed reveal miR301a’s potential mechanism. (3) Results: significantly attenuated by KO both vivo vitro. MiR-301a can target Yin-Yang 1 (YY1), resulted YY1 up-regulation (YY1′s down-stream molecule) down-regulation. siYY1 increased expression enhanced macrophages. Meanwhile, a inhibitor agonist could attenuate accelerate, respectively, phagocytosis. (4) Conclusions: current findings indicated that plays important roles capabilities through YY1/CXCR4 pathway. Hence, might be promising therapeutic candidate for inflammatory diseases adjusting bio-functions.

Language: Английский

Transcriptional control of energy metabolism by nuclear receptors DOI
Charlotte Scholtes, Vincent Giguère

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(11), P. 750 - 770

Published: May 16, 2022

Language: Английский

Citations

79
Metabolic reprogramming in liver fibrosis DOI Creative Commons
Paul Horn, Frank Tacke

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(7), P. 1439 - 1455

Published: May 31, 2024

Chronic liver diseases, primarily metabolic dysfunction-associated steatotic disease (MASLD), harmful use of alcohol, or viral hepatitis, may result in fibrosis, cirrhosis, and cancer. Hepatic fibrogenesis is a complex process with interactions between different resident non-resident heterogeneous cell populations, ultimately leading to deposition extracellular matrix organ failure. Shifts phenotypes functions involve pronounced transcriptional protein synthesis changes that require adaptations cellular substrate metabolism, including glucose lipid resembling associated the Warburg effect cancer cells. Cell activation are regulated by stress responses, unfolded response, endoplasmic reticulum stress, autophagy, ferroptosis, nuclear receptor signaling. These crucial for inflammatory fibrogenic macrophages, lymphoid cells, hepatic stellate Modulation these pathways, therefore, offers opportunities novel therapeutic approaches halt even reverse fibrosis progression.

Language: Английский

Citations

67
A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 DOI Creative Commons
Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1371 - 1393.e7

Published: May 7, 2024

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well ameliorates established fibrosis without affecting total calorie intake. Furthermore, the blunted NASH-HCC when applied therapeutically. timing, length, number cycles type diet were critical parameters determining benefits fasting. Combined proteome, transcriptome, metabolome analyses peroxisome-proliferator-activated receptor alpha (PPARα) glucocorticoid-signaling-induced PCK1 act co-operatively hepatic executors response. In line with this, PPARα targets reduced human NASH. Notably, only initiated during active phase mice robustly induced glucocorticoid signaling free-fatty-acid-induced signaling. However, hepatocyte-specific deletion partially abrogated contrast, combined knockdown Ppara Pck1 vivo abolished beneficial outcomes against inflammation fibrosis. Moreover, overexpression alone or together lowered triglycerides steatosis. Our data support notion is a promising intervention subsequent liver cancer.

Language: Английский

Citations

30
Liver diseases: epidemiology, causes, trends and predictions DOI Creative Commons

Can Gan,

Yuan Yuan, Haiyuan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Citations

3
Physiological role of cytokines in the regulation of mammalian metabolism DOI Open Access
Axel De Baat, Beckey Trinh, Helga Ellingsgaard

et al.

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(8), P. 613 - 627

Published: July 7, 2023

Language: Английский

Citations

28
Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance DOI Creative Commons
Giorgio Caratti, Ulrich Stifel, Bozhena Caratti

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 20, 2023

Abstract Insulin resistance (IR) during obesity is linked to adipose tissue macrophage (ATM)-driven inflammation of tissue. Whether anti-inflammatory glucocorticoids (GCs) at physiological levels modulate IR unclear. Here, we report that deletion the GC receptor (GR) in myeloid cells, including macrophages mice, aggravates obesity-related by enhancing due decreased ATM leading exaggerated lipolysis and severe hepatic steatosis. In contrast, GR Kupffer cells alone does not alter IR. Co-culture experiments show absence directly causes reduced phospho-AKT glucose uptake adipocytes, suggesting an important function ATM. GR-deficient are refractory alternative ATM-inducing IL-4 signaling, STAT6 chromatin loading diminished enhancer activation. We demonstrate has limiting promote insulin sensitivity.

Language: Английский

Citations

23
Macrophages and T cells in metabolic disorder-associated cancers DOI
Daniel Taranto, Daan J. Kloosterman, Leila Akkari

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

9
Circadian disruption of feeding-fasting rhythm and its consequences for metabolic, immune, cancer, and cognitive processes DOI Creative Commons
Manuel Tomás Crespo, Laura Lucía Trebucq,

Camila Agustina Senna

et al.

Biomedical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 100827 - 100827

Published: Jan. 1, 2025

The circadian system is composed by a central hypothalamic clock at the suprachiasmatic nuclei (SCN) that communicates with peripheral oscillators for daily coordination of behavior and physiology. SCN entrain to environmental 24-h light-dark (LD) cycle drive rhythms internal synchronizers such as core body temperature, hypothalamic-hypophysary hormones, sympathetic/parasympathetic activity, well behavioral feeding-fasting rhythms, which supply signals setting molecular clocks tissues. Steady phase relationships between keep homeostatic processes microbiota/microbiome composition/activity, metabolic supply/demand, energy balance, immunoinflammatory process, sleep amount quality, psychophysiological stress, etc. Indeed, risk health alterations increase when these are chronically changed prompting disruption (CD), occurring after sudden LD changes (so-called jet-lag), or due activity/feeding-rest/fasting rhythm respect cycles (as humans subjected nightwork, restricting food access rest in mice). Typical pathologies observed animal models CD epidemiological studies include syndrome, type-2 diabetes, obesity, chronic inflammation, cancer, disruption, decrease physical cognitive performance, mood, among others. present review discusses different aspects physiological dysregulations having altered potential translation human health.

Language: Английский

Citations

1
The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review DOI Open Access
Celeste M. Lavallee, Andreina Bruno, Christopher Ma

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(21), P. 4655 - 4655

Published: Nov. 3, 2022

Intermittent fasting is a non-pharmacological dietary approach to management of obesity and metabolic syndrome, involving periodic intervals complete or near-complete abstinence from food energy-containing fluids. This strategy has recently gained significant popularity in mainstream culture been shown induce weight loss humans, reduce gut systemic inflammation, improve microbial diversity dysbiosis (largely animal models). It hypothesized that intermittent could be beneficial the nonalcoholic fatty liver disease, given condition's association with obesity. review summarizes protocols, potential mechanisms action, evidence for disease. also highlights practical considerations implementing clinical practice. A search literature English-language articles related time-restricted feeding disease was completed PubMed Google Scholar. Potential action effects included modulation circadian rhythm, adipose tissue adipokines, microbiome, autophagy. Preclinical, epidemiological, trial data suggested benefits on inflammatory markers humans. However, there paucity its patients More studies are needed determine evaluate safety efficacy this population.

Language: Английский

Citations

31
Macrophage and T cell networks in adipose tissue DOI
Ramiah Jacks, Carey N. Lumeng

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 50 - 61

Published: Oct. 23, 2023

Language: Английский

Citations

22