Abstract
Diets high in saturated fatty acids (FA) represent a risk factor for the development of obesity and associated metabolic disorders, partly through their impact on the epithelial cell barrier integrity. We hypothesized that unsaturated FA could alleviate saturated FA-induced endoplasmic reticulum (ER) stress occurring in intestinal secretory goblet cells, and consequently the reduced synthesis and secretion of mucins that form the protective mucus barrier. To investigate this hypothesis, we treated well-differentiated human colonic LS174T goblet cells with palmitic acid (PAL)—the most commonly used inducer of lipotoxicity in in vitro systems—or n-9, n-6, or n-3 unsaturated fatty acids alone or in co-treatment with PAL, and measured the impact of such treatments on ER stress and Muc2 production. Our results showed that only eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids protect goblet cells against ER stress-mediated altered Muc2 secretion induced by PAL, whereas neither linolenic acid nor n-9 and n-6 FA are able to provide such protection. We conclude that EPA and DHA could represent potential therapeutic nutrients against the detrimental lipotoxicity of saturated fatty acids, associated with type 2 diabetes and obesity or inflammatory bowel disease. These in vitro data remain to be explored in vivo in a context of dietary obesity.
Highlights
Obesity is a complex and multifactorial pathology that is linked to low-grade systemic inflammation, which is identified as a key factor in its development and of related metabolic disorders [1,2]
Since an HF diet was reported to induce a strong colon mucus layer thickness decrease in mice [11,39], we first wanted to assess the effects of palmitic acid (PAL) on Muc2 and KLF4 mRNA expressions and its impact on Muc2 secretion, the main mucin secreted by the LS174T cell line
PAL affects secretion of the Muc2 protein by LS174T cells, Muc2 quantification was performed in the culture medium after 24 h of treatment
Summary
Obesity is a complex and multifactorial pathology that is linked to low-grade systemic inflammation, which is identified as a key factor in its development and of related metabolic disorders [1,2]. Systemic inflammation has been shown to be closely related to intestinal microbiota dysbiosis during high-fat (HF) feeding in both mice [3] and humans [4]. A strong increase of gut permeability [5,6] associated with systemic inflammation is partly attributed to the downregulation of genes encoding tight junctions, such as zonula-occludens 1 and occludin [6,7]. The major macromolecular component of this thick barrier is the glycoprotein Muc, produced by the intestinal goblet cells [9]. Muc contains a protein core with cysteine-rich and highly
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