scholarly journals Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 310 ◽  
Author(s):  
Camille Desgrouas ◽  
Alice-Anaïs Varlet ◽  
Anne Dutour ◽  
Damien Galant ◽  
Françoise Merono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Replication Capacity ◽  
Lamin A ◽  
Alcoholic Fatty Liver ◽  
Cellular Models ◽  
Onset Of Diabetes ◽  
Senescence Rate ◽  
Cellular Phenotypes ◽  
Subcutaneous Adipose

This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in LMNA, c.1745G>T p.(Arg582Leu), and c.1892G>A p.(Gly631Asp), in two patients with early onset of diabetes mellitus, hypertriglyceridemia and non-alcoholic fatty liver disease. In these two patients, subcutaneous adipose tissue was persistent, at least on the abdomen, and the serum leptin level remained in the normal range. Cellular studies showed elevated nuclear anomalies, an accelerated senescence rate and a decrease of replication capacity in patient cells. In cellular models, the overexpression of mutated prelamin A phenocopied misshapen nuclei, while the partial reduction of lamin A expression in patient cells significantly improved nuclear morphology. Altogether, these results suggest a link between lamin A mutant expression and senescence associated phenotypes. Transcriptome analysis of the whole subcutaneous adipose tissue from the two patients and three controls, paired for age and sex using RNA sequencing, showed the up regulation of genes implicated in immunity and the down regulation of genes involved in development and cell differentiation in patient adipose tissue. Therefore, our results suggest that some mutations in LMNA are associated with severe metabolic phenotypes without subcutaneous lipoatrophy, and are associated with nuclear misshaping.

scholarly journals Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Zhu ◽  
Jiao Xu ◽  
Dong Zhang ◽  
Xingyu Mu ◽  
Yi Shi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Alcoholic Fatty Liver ◽  
Subcutaneous Adipose ◽  
Alcoholic Fatty Liver Disease

The prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is increasing and there is an urgent need for new treatment strategy to prevent progression of hepatic steatosis and fibrosis. We have performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of hepatic steatosis and fibrosis in patients with T2DM and NAFLD. The PubMed, Web of Science, Scopus, Embase and Cochrane Central Register of Controlled Trials databases were searched for articles that met the eligibility criteria to explore the efficacy and safety of GLP-1RAs in patients with T2DM and NAFLD. We assessed pooled data using a random/fixed-effects model according to the I2 and p-values. Eight trials that included a total of 468 participants were eligible for inclusion in the review. For primary outcomes, administration of GLP-1RAs significantly decreased the content of intrahepatic adipose (IHA)[p=0.007, weight mean difference (WMD) -3.01, 95% confidence interval (CI) -4.75, -1.28], subcutaneous adipose tissue (SAT) (p<0.00001,WMD -28.53,95%CI -68.09,-26.31), and visceral adipose tissue (VAT) (p<0.0001,WMD -29.05,95%CI -42.90,-15.9). For secondary outcomes, GLP-1RAs produced a significant decrease in levels of alanine aminotransferase(ALT)(p=0.02, WMD -3.82, 95%CI -7.04, -0.60), aspartate aminotransferase (AST) (p=0.03, WMD -2.4, 95%CI -4.55,-0.25, I2 = 49%), body weight (p<0.00001,WMD -3.48,95%CI -4.58,-2.37), body mass index (p<0.00001,WMD -1.07,95%CI -1.35,-0.78), circumference waist (p=0.0002,WMD -3.87, 95%CI -5.88, -1.86) fasting blood glucose (p=0.02, WMD -0.35, 95%CI -0.06, -0.05), HbA1c (p<0.00001,WMD -0.39,95%CI -0.56,-0.22), HoMA-IR(p=0.005, WMD-1.51, 95%CI-0.87,-0.16), total cholesterol (p=0.0008, WMD -0.31, 95%CI -0.48, 0.13) and triglycerides (p=0.0008, WMD -0.27, 95%CI -0.43,-0.11) in comparison with the control regimens. The main adverse events associated with GLP-1RAs included mild-to-moderate gastrointestinal discomfort and nonsense hypoglycemia that resolved within a few weeks. GLP-1RAs were an effective treatment that improved intrahepatic visceral and subcutaneous adipose tissue, inflammatory markers, the anthropometric profiles and some metabolic indices in patients with T2DM and NAFLD, GLP-1RAs could be considered for use in these if there are no contraindications. Further studies are needed to understand the direct and indirect effects of GLP-1RAs on NAFLD and the potential mechanism via which they prevent its progression.Systematic Review Registration: PROSPERO, identifier CRD42021265806.

Abstract 19405: Association of Deep and Superficial Abdominal Subcutaneous Tissue With Hepatic Fat Content

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Inge v Munckhof ◽  
Tessa Brand ◽  
Marinette v Graaf ◽  
Jacqueline d Graaf ◽  
Joost Rutten
Keyword(s):  
Adipose Tissue ◽  
Alcohol Use ◽  
Hepatic Steatosis ◽  
Subcutaneous Adipose Tissue ◽  
Large Population ◽  
Univariate Analysis ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Subcutaneous Adipose

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Visceral adipose tissue (VAT) is regarded to be an important factor in the pathogenesis of NAFLD. Subcutaneous adipose tissue (SAT) is separated by the fascia superficialis into the deep SAT (dSAT) and superficial SAT (sSAT). It has been suggested that dSAT is related to an increased risk for obesity related complications, whereas sSAT has a more favorable profile. The aim of this study was to investigate the association of superficial and deep subcutaneous adipose tissue with hepatic steatosis. Methods: We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 133 subjects, BMI > 27 kg/m 2 , aged 55-81 years. Abdominal magnetic resonance imaging was performed at level L4-L5 to measure VAT, dSAT and sSAT volumes. The amount of liver fat was quantified by MR spectroscopy. Results: Men had significantly higher volumes of VAT and lower volumes of sSAT compared with women. No differences in volumes of dSAT were observed. In univariate analysis, the VAT volume was found to be correlated with hepatic steasosis (r = 0.339; p <0.001), while no significant correlation was found between total SAT, sSAT or dSAT with hepatic steatosis. After adjustment for age, alcohol use and sex, VAT was still positively correlated with hepatic steatosis with a standardized β of 0,276 (p=0.007), and sSAT, but not total SAT or dSAT, was negatively correlated with hepatic steatosis with a standardized β of -0,363 (p=0.033). Conclusions: VAT as measured by MRI is positively correlated with hepatic steatosis, in contrast to sSAT which is negatively correlated after adjustment for age, alcohol use and sex. We found no significant correlation between total SAT or dSAT and hepatic steatosis.

Insulin resistance, systemic and regional inflammation in subcutaneous adipose tissue during weight loss in a population with obesity

2019 ◽  
Author(s):  
Frederique Van de Velde ◽  
Margriet Ouwens ◽  
Arsene-Helene Batens ◽  
Samyah Shadid ◽  
Bruno Lapauw ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Subcutaneous Adipose

701-P: Effects of Exercise on Extracellular Matrix Modifiers in Subcutaneous Adipose Tissue of Obese Adults

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 701-P
Author(s):  
PALLAVI VARSHNEY ◽  
BENJAMIN J. RYAN ◽  
CHIWOON AHN ◽  
MICHAEL W. SCHLEH ◽  
JEFFREY F. HOROWITZ
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Obese Adults ◽  
Subcutaneous Adipose
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