scholarly journals Molecular and Cellular Bases of Lipodystrophy Syndromes

2022 ◽  
Vol 12 ◽  
Author(s):  
Jamila Zammouri ◽  
Camille Vatier ◽  
Emilie Capel ◽  
Martine Auclair ◽  
Caroline Storey-London ◽  
...  

Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3300
Author(s):  
Xiaoxiao Wang ◽  
Huiying Rao ◽  
Feng Liu ◽  
Lai Wei ◽  
Honggui Li ◽  
...  

Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3342
Author(s):  
Alina Kurylowicz

In recent years, there has been a large amount of evidence on the role of microRNA (miRNA) in regulating adipose tissue physiology. Indeed, miRNAs control critical steps in adipocyte differentiation, proliferation and browning, as well as lipolysis, lipogenesis and adipokine secretion. Overnutrition leads to a significant change in the adipocyte miRNOME, resulting in adipose tissue dysfunction. Moreover, via secreted mediators, dysfunctional adipocytes may impair the function of other organs and tissues. However, given their potential to control cell and whole-body energy expenditure, miRNAs also represent critical therapeutic targets for treating obesity and related metabolic complications. This review attempts to integrate present concepts on the role miRNAs play in adipose tissue physiology and obesity-related dysfunction and data from pre-clinical and clinical studies on the diagnostic or therapeutic potential of miRNA in obesity and its related complications.


2021 ◽  
Vol 12 ◽  
Author(s):  
Somaya Albhaisi ◽  
Mazen Noureddin

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. Inflammation plays a key role in the progression of NASH and can be provoked by intrahepatic (e.g., lipotoxicity, immune responses, oxidative stress and cell death) and extrahepatic sources (adipose tissue or gut). The identification of triggers of inflammation is central to understanding the mechanisms in NASH development and progression and in designing targeted therapies that can halt or reverse the disease. In this review, we summarize the current and potential therapies targeting inflammation in NASH.


2021 ◽  
Author(s):  
Kabelo Mokgalaboni ◽  
Yonela Ntamo ◽  
Khanyisani Ziqubu ◽  
Tawanda M Nyambuya ◽  
Bongani Nkambule ◽  
...  

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In...


2019 ◽  
Vol 39 (03) ◽  
pp. 291-300 ◽  
Author(s):  
Hannelie Korf ◽  
Markus Boesch ◽  
Lore Meelberghs ◽  
Schalk van der Merwe

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liver as a result of innate immune cell activation and/or hepatocyte injury. Additionally, they may originate from other sites such as adipose tissue or the intestinal tract. In the current review, the authors will primarily focus on events within adipose tissue which may be of importance in triggering the disease progression. They specifically focus on the role of adipose tissue macrophages during NAFLD pathogenesis and how microenvironmental factors may shape their metabolic profile. They further dissect how redirecting the macrophage's metabolic profile alters their immunological functions. Finally, they discuss the opportunities and challenges of targeting macrophages to interfere in disease progression.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yuka Murata ◽  
Takashi Yamashiro ◽  
Takaomi Kessoku ◽  
Israt Jahan ◽  
Haruki Usuda ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of liver pathologies, from simple steatosis to steatohepatitis. Recent studies have increasingly noted the aberrant expression of microRNAs closely related to NAFLD pathologies. We have previously shown the presence of increased levels of microRNA-27b (miR-27b) in patients with NAFLD. In this study, we investigated the role of miR-27b in NAFLD by examining the impact of up-regulated miR-27b on the differentiation of preadipocytes into mature adipocytes. We found that miR-27b-3p remarkably enhances the adipocyte differentiation of 3T3-L1 cells associated with lipid accumulation and intracellular triglyceride contents. Furthermore, we have demonstrated not only that miR-27b-3p induces acyl-CoA thioesterase 2 (ACOT2) expression in 3T3-L1 cells, but also that the knockdown of ACOT2 suppresses lipid accumulation and adipocyte differentiation in both the presence and absence of miR-27b-3p treatment. Our data strongly suggest that the miR-27b-ACOT2 axis is an important pathway in adipocyte differentiation and may play a role in the pathogenesis of NAFLD.


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