scholarly journals A Review of FoxO1-Regulated Metabolic Diseases and Related Drug Discoveries

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 184 ◽  
Author(s):  
Shiming Peng ◽  
Wei Li ◽  
Nannan Hou ◽  
Niu Huang
Keyword(s):  
Transcription Factor ◽  
Liver Disease ◽  
Energy Metabolism ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Alcoholic Fatty Liver ◽  
Related Drug ◽  
Alcoholic Fatty Liver Disease

FoxO1 is a conserved transcription factor involved in energy metabolism. It is tightly regulated by modifications on its mRNA and protein and responds to environmental nutrient signals. FoxO1 controls the transcription of downstream genes mediating metabolic regulation. Dysfunction of FoxO1 pathways results in several metabolic diseases, including diabetes, obesity, non-alcoholic fatty liver disease, and atherosclerosis. Here, we summarize the mechanism of FoxO1 regulation behind these diseases and FoxO1-related drug discoveries.

scholarly journals Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1903
Author(s):  
Tae Hyun Kim ◽  
Dong-Gyun Hong ◽  
Yoon Mee Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Signaling Crosstalk ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The liver plays a key role in maintaining energy homeostasis by sensing and responding to changes in nutrient status under various metabolic conditions. Recently highlighted as a major endocrine organ, the contribution of the liver to systemic glucose and lipid metabolism is primarily attributed to signaling crosstalk between multiple organs via hepatic hormones, cytokines, and hepatokines. Hepatokines are hormone-like proteins secreted by hepatocytes, and a number of these have been associated with extra-hepatic metabolic regulation. Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease. In this review, we describe the hepatokine-driven inter-organ crosstalk in the context of liver pathophysiology, with a particular focus on NAFLD progression. Moreover, we summarize key hepatokines and their molecular mechanisms of metabolic control in non-hepatic tissues, discussing their potential as novel biomarkers and therapeutic targets in the treatment of metabolic diseases.

scholarly journals Non-alcoholic fatty liver disease: current aspects of diagnosis in real clinical practice

2021 ◽  
Vol 2 (4) ◽  
pp. 40-50
Author(s):  
Dmitry I. Trukhan ◽  
Keyword(s):  
Clinical Practice ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Diagnostic Algorithm ◽  
Malignant Neoplasms ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Real Clinical Practice

In the diagnosis and subsequent supervision of patients with non-alcoholic fatty liver disease (NAFLD) and obesity in real clinical practice, the role and importance of the doctor of first contact (therapist and general practitioner) increases. Non-alcoholic fatty liver disease is currently considered as the hepatic component of metabolic syndrome. A diagnostic algorithm for NAFLD at the stage of primary health care is presented. The most difficult question at 2–4 levels of the diagnostic algorithm is the differential diagnosis between NAFLD and alcoholic liver disease. During a pandemic of a novel coronavirus infection (COVID-19), patients with NAFLD or NASH, as a rule, have concomitant metabolic diseases such as diabetes mellitus, arterial hypertension and obesity, and also have to take a large number of potentially hepatotoxic drugs, it is advisable to classify them as elevated risk of infection with SARS-CoV-2, and the severe course of this infection. This allows us to consider NAFLD as dangerous in terms of the severe course of COVID-19, as viral hepatitis, autoimmune hepatitis and liver fibrosis / cirrhosis. It is known that NAFLD is an independent predictor of not only high cardiovascular risks, but also hepatocellular carcinoma and malignant neoplasms of various localization, as well as a number of other comorbid conditions. The review concludes with a clinical observation illustrating the difficulty of early diagnosis of intrahepatic cholangiocarcinoma in a patient with NAFLD and other metabolic risk factors.

scholarly journals NON-ALCOHOLIC FATTY LIVER DISEASE IN THE CONTEXT OF ALTERED GUT MICROBIOTA

2021 ◽  
Vol 74 (4) ◽  
pp. 1007-1010
Author(s):  
Tetyana V. Koval ◽  
Ivan V. Chopey ◽  
Mykhaylo M. Hechko ◽  
Artur V. Kurakh
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Intestinal Microbiome ◽  
Alcoholic Fatty Liver ◽  
Physiological Processes ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota. Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed. Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.

scholarly journals Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish

PLoS Genetics ◽  
2014 ◽  
Vol 10 (5) ◽  
pp. e1004335 ◽  
Author(s):  
Deanna L. Howarth ◽  
Claudia Lindtner ◽  
Ana M. Vacaru ◽  
Ravi Sachidanandam ◽  
Orkhontuya Tsedensodnom ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Activating Transcription Factor ◽  
Necessary And Sufficient ◽  
Alcoholic Fatty Liver Disease

scholarly journals The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 662
Author(s):  
Roberta Forlano ◽  
Benjamin H. Mullish ◽  
Lauren A. Roberts ◽  
Mark R. Thursz ◽  
Pinelopi Manousou
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Gut Permeability ◽  
Alcoholic Fatty Liver ◽  
Treatment Pathways ◽  
New Treatment ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.

scholarly journals Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 872 ◽  
Author(s):  
Jinchunzi Yang ◽  
Marta Fernández-Galilea ◽  
Leyre Martínez-Fernández ◽  
Pedro González-Muniesa ◽  
Adriana Pérez-Chávez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Omega 3 ◽  
Alcoholic Fatty Liver ◽  
Pufa Supplementation ◽  
Alcoholic Fatty Liver Disease

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

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