Abstract
The small intestine is crucial for lipid homeostasis and immune regulation of the whole body. Endoplasmic reticulum (ER) stress may affect lipid metabolism and inflammation in the intestine, but the potential mechanism is not completely understood. In the present study, intraperitoneal injection of tunicamycin (TM) induced ER stress in the intestine of large yellow croaker (Larimichthys crocea). ER stress induced excessive accumulation of triglyceride (TG) in the intestine by promoting lipid synthesis. However, it also enhanced lipid secretion and fatty acid β-oxidation. In addition, ER stress augmented inflammation in the intestine by promoting p65 into the nucleus and increasing proinflammatory genes expression. In the isolated intestinal cells, the obtained results showed that TM treatment significantly upregulated the mRNA expression of lipid synthesis and inflammatory response genes, which were consistent with those in vivo. Moreover, overexpression of unfolded protein response (UPR) sensors significantly upregulated promoter activities of lipid synthesis and proinflammatory genes. In conclusion, the results suggested that ER stress disturbed lipid metabolism and augmented inflammation in the intestine and isolated intestinal cells of large yellow croaker, which may contribute to finding novel therapies to tackle lipid dysregulation and inflammation in the intestine of fish and human beings.
Highlights
The small intestine is abundant in intestinal microvilli composed of enterocytes, goblet cells, and enteroendocrine cells [1]
Compared with the control group, the mRNA expression of Endoplasmic reticulum (ER) stress-related genes including grp78, xbp1s, atf4, atf6, and chop was significantly increased in the intestine after TM injection (P < 0.05) (Figure 1A)
The protein levels of glucose-regulated protein 78 (GRP78), X-boxbinding protein 1 s (XBP1s), and p-protein kinase-like ER kinase (PERK) were significantly upregulated (P < 0.05), while the protein level of ATF6 was not significantly changed in the TM group (P > 0.05) (Figure 1B). These results indicated that TM injection induced ER stress in the intestine of large yellow croaker in vivo
Summary
The small intestine is abundant in intestinal microvilli composed of enterocytes, goblet cells, and enteroendocrine cells [1]. The lipid metabolism in the intestine is complicated, including uptake of lipids, lipid synthesis, chylomicrons secretion, cytoplasmic lipid droplets storage, and fatty acid b-oxidation [3]. The endoplasmic reticulum (ER) is important for regulating protein folding, macromolecule biosynthesis, and calcium storage. The UPR sensors have been proved to play a crucial role in regulating lipid metabolism [6]. Hepatic-specific deletion of IRE1a increased the peroxisome proliferator-activated receptor g (PPARg) level to increase the hepatic lipid content [7]. The activation of the PERK pathway increased lipid accumulation in cells by activating sterol regulatory element binding protein 1c (SREBP-1c) [8]. Chen et al [9] found that ATF6 increases fatty acid b-oxidation through peroxisome proliferator-activated receptor a (PPARa). Numerous studies have investigated the mechanism of ER stress affecting hepatic lipid homeostasis, the mechanism of ER stress-mediated intestinal lipid metabolism is not completely understood
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