Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Therapeutics and Clinical Risk Management, Год журнала: 2023, Номер Volume 19, С. 77 - 96

Опубликована: Янв. 1, 2023

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent without any approved treatment to-date despite intensive research efforts by researchers and pharmaceutical industry.Fibroblast growth factor (FGF)-21 has been gaining increasing attention as possible contributing thus therapeutic target for obesity-related metabolic disorders, including NAFLD, mainly due to its effects on lipid carbohydrate metabolism.Most animal human observational studies have shown higher FGF-21 concentrations in NAFLD than non-NAFLD, implying that may be increased counteract hepatic steatosis inflammation.However, although Mendelian Randomization revealed variations of levels within the physiological range hyperlipidemia possibly nonalcoholic steatohepatitis, they also indicate FGF-21, concentrations, fail reverse not able control obesity other diseases, indicating state resistance or insensitivity could respond administration supraphysiological concentrations.Interventional with analogs (eg, pegbelfermin, efruxifermin, BOS-580) humans provided some favorable results Phase 1 2 studies.However, definite effect clarified after completion ongoing clinical trials paired biopsies histological endpoints.The aim this review critically summarize experimental data an attempt highlight existing knowledge areas uncertainty, subsequently, focus potential NAFLD.

Язык: Английский

---

The role of lipid metabolism in osteoporosis: Clinical implication and cellular mechanism

Genes & Diseases, Год журнала: 2023, Номер 11(4), С. 101122 - 101122

Опубликована: Сен. 21, 2023

In recent years, researchers have become focused on the relationship between lipids and bone metabolism balance. Moreover, many diseases related to lipid disorders, such as nonalcoholic fatty liver disease, atherosclerosis, obesity, menopause, are associated with osteoporotic phenotypes. It has been clinically observed in humans that these disorders promote changes osteoporosis-related indicators mineral density mass. Furthermore, similar phenotype were high-fat high-cholesterol-induced animal models. Abnormal (such increased oxidized elevated plasma cholesterol) affects microenvironment homeostasis via cross-organ communication, promoting differentiation of mesenchymal stem cells adipocytes, inhibiting commitment towards osteoblasts. disturbances affect balance by secretion cytokines receptor activator nuclear factor-kappa B ligand osteoblasts stimulating osteoclasts. Conclusively, this review addresses possible link osteoporosis elucidates potential modulatory mechanisms signaling pathways which We also summarize approaches prospects intervening for treatment.

Язык: Английский

---

Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7517 - 7517

Опубликована: Апрель 19, 2023

Chronic liver disease (CLD), including non-alcoholic fatty (NAFLD) and its advanced form, steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in liver, while NASH associated with inflammation damage. Osteosarcopenia, which combines muscle bone mass loss, an emerging clinical problem chronic that often underappreciated. The reductions share several common pathophysiological pathways; insulin resistance systemic are most crucial predisposing factors related to presence gravity worsening outcome disease. This article explores relationship between osteosarcopenia NAFLD/MAFLD, focusing on diagnosis, prevention treatment this condition patients CLD.

Язык: Английский

---

Osteoprotegerin/Receptor Activator of Nuclear Factor-Kappa B Ligand/Receptor Activator of Nuclear Factor-Kappa B Axis in Obesity, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

Current Obesity Reports, Год журнала: 2023, Номер 12(2), С. 147 - 162

Опубликована: Май 19, 2023

Abstract Purpose of Review To summarize evidence on the potential involvement osteoprotegerin (OPG)/receptor activator nuclear factor-kappa B (NF-κΒ) ligand (RANKL)/receptor NF-κΒ (RANK) axis in pathogenesis metabolic diseases. Recent Findings The OPG-RANKL-RANK axis, which has been originally involved bone remodeling and osteoporosis, is now recognized as a contributor obesity its associated comorbidities, i.e., type 2 diabetes mellitus nonalcoholic fatty liver disease. Besides bone, OPG RANKL are also produced adipose tissue may be inflammatory process with obesity. Metabolically healthy lower circulating concentrations, possibly representing counteracting mechanism, while elevated serum levels reflect an increased risk dysfunction or cardiovascular have proposed regulators glucose metabolism potentially mellitus. In clinical terms, consistently concentrations. With regard to disease, experimental data suggest contribution hepatic steatosis, inflammation, fibrosis; however, most studies showed reduction concentrations RANKL. Summary emerging comorbidities warrants further investigation by mechanistic diagnostic therapeutic implications.

Язык: Английский

---

Association of chronic liver disease with bone diseases and muscle weakness

Journal of Bone and Mineral Metabolism, Год журнала: 2024, Номер 42(4), С. 399 - 412

Опубликована: Фев. 1, 2024

Язык: Английский

---

Osteokines in Nonalcoholic Fatty Liver Disease

Current Obesity Reports, Год журнала: 2024, Номер unknown

Опубликована: Сен. 3, 2024

Язык: Английский

---

Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2

Bone Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 30, 2025

Abstract The delicate balance between bone formation by osteoblasts and resorption osteoclasts maintains homeostasis. Nuclear receptors (NRs) are now understood to be crucial in physiology pathology. However, the function of Farnesoid X receptor (FXR), a member NR family, regulating homeostasis remains incompletely understood. In this study, vitro vivo models revealed delayed development an osteoporosis phenotype mice lacking FXR marrow mesenchymal stem cells (BMSCs) due impaired osteoblast differentiation. Mechanistically, could stabilize RUNX2 inhibiting Thoc6-mediated ubiquitination, thereby promoting osteogenic activity BMSCs. Moreover, activated directly bind Thoc6 promoter, suppressing its expression. interaction was mediated Runt domain WD repeat Thoc6. Additionally, Obeticholic acid (OCA), orally available agonist, ameliorate loss ovariectomy (OVX)-induced osteoporotic mouse model. Taken together, our findings suggest that plays pivotal roles differentiation stability targeting may promising therapeutic approach for osteoporosis.

Язык: Английский

---

Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease

Hepatology International, Год журнала: 2022, Номер 17(2), С. 357 - 366

Опубликована: Дек. 15, 2022

Язык: Английский

---

Regulation of the immune microenvironment by pioglitazone-loaded polylactic glycolic acid nanosphere composite scaffolds to promote vascularization and bone regeneration

Journal of Tissue Engineering, Год журнала: 2024, Номер 15

Опубликована: Янв. 1, 2024

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration blood vessels, other factors must be considered in tissue engineering. To effectively repair defect, it important to decrease excessive inflammation, enhance into osteoblasts, stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), gelatin (GEL) scaffolds were produced using 3D printing technology pioglitazone (PIO)-containing polylactic acid–glycolic acid (PLGA) nanospheres added. In both vitro vivo studies, material with PIO-loaded could reduce response encouraging macrophage polarization from M1 M2 promoting BMSCs activating BMP2/Smad/RUNX2 signal pathway defects. The vascularization human umbilical vein endothelial (HUVECs) through PI3K/AKT/HIF1-/VEGF was also encouraged. research PIO-containing PLGA revealed massive collagen deposition skin models. These findings indicate a potentially effective scaffold for healing, when nanospheres—which contain drug PIO—are combined ATP/PVA/GEL scaffolds.

Язык: Английский

---

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Март 8, 2024

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into most common chronic globally, affecting 17-38% of general population and 50-75% patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum diseases, ranging from simple steatosis (non-alcoholic liver, NAFL) steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis cirrhosis failure or/and hepatocellular carcinoma. Due its increasing prevalence associated morbidity mortality, disease-related broader socioeconomic burden is substantial. Of note, currently there no globally approved pharmacotherapy for NAFLD. Similar NAFLD, osteoporosis constitutes also silent disease, until an osteoporotic fracture occurs, which poses markedly significant burden. Increasing emerging data have recently highlighted links between osteoporosis, linking pathogenesis process bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence needed towards discovering potential causative links. Since these two diseases frequently co-exist, suggesting that anti-osteoporosis treatments may affect progression by impacting on pathogenetic mechanisms. In present review, we overview current understanding liver-bone cross talk summarize experimental correlating focusing possible effects anti-osteoporotic drugs

Язык: Английский

---