A Distinctive NAFLD Signature in Adipose Tissue from Women with Severe Obesity

Abstract

Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.

Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach

“…Following functional enrichment analysis, the upregulated DEGs were involved in hormone response, cellular response to fatty acids, regulation of adipocyte differentiation, positive regulation of Akt signaling, and regulation of cell adhesion, which are in line with the previous findings. The disease–gene interactions further revealed several conditions, some of which are known to be associated with obesity, such as heart disease, fatty liver disease [ 16 ], and nephropathy.…”

“…It is already known that VAT exosomes can induce TGF-β pathway dysregulation in hepatocytes in vitro, indicative of a possible role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) [ 19 ]. Recently, a distinctive NAFLD-associated transcriptomic signature, which included a highly expressed TGF-β1, has been reported in the white AT of severely obese females [ 16 ]. Besides vascular inflammation, weight gain, kidney failure, and liver and heart diseases, the disease–gene interaction also revealed unipolar depression, various cancers, and scoliosis, all known risks for obese children [ 3 , 20 , 21 ].…”

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

“…Recently, some authors have suggested that SFRP5 is a protective adipokine with an anti-inflammatory role in NAFLD pathogenesis [ 7 , 20 ]; however, inconclusive results have been reported. In this sense, given that the adipose tissue-liver axis seems to be relevant in the progression of NAFLD [ 16 ], in this study, we evaluated the SFRP5/WNT5A-PPARγ pathway in adipose tissue samples of women with different degrees of NAFLD associated to obesity.…”

“…In other ways, the expression of SFRP5 in adipose tissue of NAFLD patients it could be also increased by the liver disease itself given the intercommunication between both tissues [ 16 ]. Since obesity has been suggested to induce SFRP5 expression in mice and humans [ 64 ], we hypothesize that NAFLD may result in the same effect by increasing metabolic imbalance.…”

“…The most important functions of adipose tissue are storing the body’s excess energy and acting as an endocrine organ for the regulation of metabolic homeostasis through the release of hormones and adipokines [ 10 , 11 ]. While VAT drains directly to the portal circulation of the liver [ 12 ] and seems to be directly associated with hepatic steatosis, liver inflammation and fibrosis [ 13 , 14 , 15 ], the relationship between SAT and NAFLD seems to lie in the transcriptome and macrophage phenotype [ 16 ].…”