Dataset Information

Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress.

ABSTRACT: Recent evidences have linked indole-3-acetic acid (IAA), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However, data supporting IAA-mediated protection against nonalcoholic fatty liver disease (NAFLD) from an in vivo study is lacking. In this study, we assessed the role of IAA in attenuating high-fat diet (HFD)-induced NAFLD in male C57BL/6 mice. Administration of IAA (50 mg/kg body weight) by intraperitoneal injection was found to alleviate HFD-induced elevation in fasting blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index as well as plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), and glutamic-pyruvic transaminase (GPT) activity. Histological examination further presented the protective effect of IAA on liver damage induced by HFD feeding. HFD-induced an increase in liver total triglycerides and cholesterol, together with the upregulation of genes related to lipogenesis including sterol regulatory element binding-protein 1 (Srebf1), steraroyl coenzyme decarboxylase 1 (Scd1), peroxisome proliferator-activated receptor gamma (PPAR?), acetyl-CoA carboxylase 1 (Acaca), and glycerol-3-phosphate acyltransferase, mitochondrial (Gpam), which were mitigated by IAA treatment. The results of reactive oxygen species (ROS) and malonaldehyde (MDA) level along with superoxide dismutase (SOD) activity and glutathione (GSH) content in liver tissue evidenced the protection of IAA against HFD-induced oxidative stress. Additionally, IAA attenuated the inflammatory response of liver in mice exposed to HFD as shown by the reduction in the F4/80-positive macrophage infiltration and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-? (TNF-?). In conclusion, our findings uncover that IAA alleviates HFD-induced hepatotoxicity in mice, which proves to be associated with the amelioration in insulin resistance, lipid metabolism, and oxidative and inflammatory stress.

SUBMITTER: Ji Y

PROVIDER: S-EPMC6769627 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress.

Ji Yun Y Gao Yuan Y Chen Hong H Yin Yue Y Zhang Weizhen W

Nutrients 20190903 9

Recent evidences have linked indole-3-acetic acid (IAA), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However, data supporting IAA-mediated protection against nonalcoholic fatty liver disease (NAFLD) from an in vivo study is lacking. In this study, we assessed the role of IAA in attenuating high-fat diet (HFD)-induced NAFLD in male C57BL/6 mice. Administration of IAA (50 mg/kg body weight) by intraperitoneal injection was found to alleviate ...[more]

PMID: 31484323

Similar Datasets

Project description:BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.

Project description:Our previous studies have reported the effect of swietenine (a major bioactive component of Swietenia macrophylla seeds) in reversing and potentiating the effect of metformin in hyperglycemia and hyperlipidaemia in diabetic rats. Moreover, we reported that the anti-inflammatory effect of swietenine is mediated via the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This study evaluated the effect of swietenine and its mechanisms in nonalcoholic fatty liver disease (NAFLD) in high-fat diet/streptozotocin-induced diabetic mice. The effect was assessed by determining blood biochemical parameters (glucose, cholesterol, triglycerides, alanine transaminase (ALT), asparate transaminase (AST), alkaline phosphatase (ALP), glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA)) and liver biochemical parameters (liver index, cholesterol, and triglycerides). Hepatic lipid accumulation (initial causative factor in NAFLD) was determined by oil-O-red staining. Gene expression (qPCR) and immunohistochemical studies were performed to elucidate the mechanism of swietenine's effect in NAFLD. The critical regulators (genes and proteins) involved in lipogenesis (ACLY, ACC1, FASN, SREBP1c, and ChREBPβ) and oxidative stress (Nrf2, NQO-1 and HO-1) pathways were determined. In mice fed with a high-fat diet followed by streptozotocin injection, the liver cholesterol, triglycerides, and lipids were elevated. These increases were reversed by the oral administration of swietenine, 80 mg/kg body weight, on alternate days for eight weeks. Gene expression and immunohistochemical studies showed that swietenine reversed the elevated levels of crucial enzymes of lipogenesis (ACLY, ACC1 and FASN) and their master transcription factors (SREBP1c and ChREBPβ). Furthermore, swietenine activated the Nrf2 antioxidant defense mechanism, as evidenced by the upregulated levels of Nrf2, NQO-1, and HO-1. It is concluded that swietenine shows beneficial effects in diabetes-induced NAFLD via inhibiting lipogenesis and activating the Nrf2 pathway.

Dataset Information

Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress.

Publications

Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets