In patients with nonalcoholic fatty liver disease (NAFLD), alterations in adipose tissue biology likely increase the release of plasminogen activator inhibitor-1 (PAI-1) and exosomes into circulation and are associated with hepatic and skeletal muscle insulin resistance, according to a study published in Gastroenterology.

Insulin resistance is a common feature of obesity and is critical in the pathogenesis of NAFLD. Hepatic steatosis, the hallmark feature of NAFLD, is also common in individuals with obesity. Therefore, it is important to understand the underlying mechanisms responsible for insulin resistance in patients with obesity and NAFLD.

Investigators studied the importance of subcutaneous abdominal adipose tissue (SAAT) inflammation and plasma and SAAT-derived exosomes in regulating insulin sensitivity in people with obesity and NAFLD (ClinicalTrials.gov Identifier: NCT02706262). A total of 70 participants were included in the study (14 men and 56 women).


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Researchers found that proinflammatory macrophages, proinflammatory CD4 and CD8 T cell populations, and gene expression of several cytokines in SAAT were greater in patients with obesity and NAFLD (OB-NAFLD) than in patients with obesity and normal intrahepatic triglyceride content (OB-NL) and lean patients with normal intrahepatic triglyceride content (LEAN).

With the exception of PAI-1, which was greater in the OB-NAFLD group than in the LEAN and OB-NL groups, 24-hour plasma cytokine concentration areas under the curve (AUCs) were not different between groups. The percentage of proinflammatory macrophages and plasma PAI-1 concentration AUCs were inversely correlated with both hepatic and whole-body insulin sensitivity. Compared with exosomes from OB-NL participants, plasma and SAAT-derived exosomes from the OB-NAFLD group decreased insulin signaling in myotubes and hepatocytes.

The authors concluded, “This clinical study demonstrates a link between insulin resistance and both adipose tissue-derived PAI-1 and exosomes in people with NAFLD, but is unable to determine whether this relationship is causal.” They added, “Our findings support the potential importance of alterations in adipose tissue biology in the pathogenesis of insulin resistance in people with obesity and NAFLD.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Fuchs A, Samovski D, Smith GI, et al. Associations among adipose tissue immunology, inflammation and exosomes and insulin sensitivity in people with obesity and nonalcoholic fatty liver disease. Gastroenterol. Published online May 15, 2021. doi: 10.1053/j.gastro.2021.05.008