Abstract
IntroductionThe immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties.AimsThis study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model.ResultsThe ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages.ConclusionOur findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.
Highlights
The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)
The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells
Under the hypothesis that a prevailing inflammatory state in NAFLD would be amplified by linoleic acid and leptin, we aimed to evaluate the effects of these molecules on the production of cytokines and reactive oxygen species in immune cells from patients with NAFLD
Summary
Blood samples and liver biopsies were collected from 72 adult patients with confirmed NAFLD at the Gastroenterology Division of the Josede San Martin (JSM) Clinical Hospital (Table 1). The experimental protocols and sample studies were approved by the Ethics Committee of the JSM Clinical Hospital at the University of Buenos Aires and followed the internationally endorsed standards as stated in the Declaration of Helsinki. All subjects were informed of the aim of the study and gave their written informed consent. We collected no more than 15 ml of blood from each patient for this project. The blood sample volume was insufficient to perform each assay in every subject, and the amount of liver biopsy tissue was inadequate for more than one assay per sample
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