Few studies on humans have comprehensively evaluated the intake composition of methyl-donor nutrients (MDNs: choline, betaine, and folate) in relation to visceral obesity (VOB)-related hepatic steatosis (HS), the hallmark of non-alcoholic fatty liver diseases. In this case–control study, we recruited 105 patients with HS and 104 without HS (controls). HS was diagnosed through ultrasound examination. VOB was measured using a whole-body analyzer. MDN intake was assessed using a validated quantitative food frequency questionnaire. After adjustment for multiple HS risk factors, total choline intake was the most significant dietary determinant of HS in patients with VOB (Beta: −0.41, p = 0.01). Low intake of choline (<6.9 mg/kg body weight), betaine (<3.1 mg/kg body weight), and folate (<8.8 μg/kg body weight) predicted increased odds ratios (ORs) of VOB-related HS (choline: OR: 22, 95% confidence interval [CI]: 6.5–80; betaine: OR: 14, 95% CI: 4.4–50; and folate: OR: 19, 95% CI: 5.2–74). Combined high intake of choline and betaine, but not folate, was associated with an 81% reduction in VOB-related HS (OR: 0.19, 95% CI: 0.05–0.69). Our data suggest that the optimal intake of choline and betaine can minimize the risk of VOB-related HS in a threshold-dependent manner.
Inhibition of acetyl-CoA carboxylase (ACC) is one approach used for treating metabolic syndrome. Using partially purified ACC to screen herbs commonly used in Taiwanese folk medicine, we previously showed that an ethanol extract of Polygonum hypoleucum Ohwi (EP) had potent ACC inhibitory activity and partially alleviated metabolic disorders induced by a high fat diet. Since ACC plays a crucial role in de novo lipogenesis, the favorable effects of EP on metabolism were tested under lipogenic conditions in the present study. On incubating high glucose (30 mM)-stimulated HepG2 cells with EP (72.5 or 145 microg/mL), ACC and fatty acid synthase activity, triacylglycerol content, and microsomal triacylglycerol transfer protein mRNA levels were all significantly reduced (P < 0.05, vs vehicle). When EP was given at low, medium, and high dosages (94, 188, and 470 mg/kg) to sucrose water-treated Wistar rats for four weeks, alleviation of symptoms associated with metabolic syndrome, including obesity, insulin resistance, hypertriglyceridemia, and hypertension, accompanied by hepatic ACC inactivation, was seen in the low dosage group. Four compounds (emodin, emodin-8-O-beta-D-glucopyranoside, (+)-catechin, and (-)-epicatechin) isolated from EP were identified as ACC inhibitors. These results confirm that P. hypoleucum Ohwi, acting partly through ACC inhibition, has favorable effects in alleviating metabolic disturbances occurring under lipogenic conditions.
The aim of this study was to investigate whether maternal ingestion of oxidized frying oil (OFO) during pregnancy influences the susceptibility to diet-induced obesity (DIO) of the adult offspring. Pregnant C57BL/6J mice were fed either a control diet [10% fresh soybean oil (SO)] or an OFO-containing diet (10% OFO) throughout the entire gestational period. After parturition, all pups were nursed by SO-fed dams for 3 wk, weaned onto a nonpurified standard diet for 4 wk, and shifted to a high-fat diet (29% butter + 1% SO) for 5 wk. Consequently, 4 groups of offspring were obtained, consisting of the male (m) or female (f) offspring of dams fed the OFO diet (OFO-m and OFO-f) or the SO diet (SO-m and SO-f). At pregnancy d 18, higher amounts (P < 0.05) of mRNA for PPARα target genes were found in the liver of the OFO-fed dams and their fetuses than in their SO controls. Although all pups were raised under the same conditions in postnatal life, a comparison based on the gender of pups from dams fed the different diets showed that adult OFO-f mice were prone to DIO, whereas adult OFO-m mice were resistant. The adult OFO-m mice also had higher expression of PPARα target genes in the liver and white adipose tissue (WAT) and of thermogenic genes in the WAT than adult SO-m mice, whereas adult OFO-f and SO-f mice did not differ. We conclude that uterine PPARα activation caused by maternal OFO ingestion affects hepatic PPARα activity and adipose thermogenic capacity and contributes to the differential susceptibility to DIO in the male and female offspring in adulthood.
Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.
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Background: Establishing animal models with metabolic disorders similar to human metabolic syndrome (MS) is important. In terms of eliciting a full array of MS, we have previously shown that Wistar rats are more responsive to sucrose water drinking than are C57BL/6J mice. This study was aimed at investigating the underlying molecular mechanism of sucrose water-induced MS in Wistar rats. Methods: Male Wistar rats were divided into 2 groups (n = 8 for each group) which were given plain water (C group) or 30% sucrose water (SW group) to drink ad libitum. After 20 weeks, the transcriptional levels and protein translocation of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate response element-binding protein (ChREBP) as well as the protein levels of protein tyrosine phosphatase-1B (PTP-1B) in insulin-responsive tissues (liver, muscle, and adipose tissue) were measured. Results: The sucrose water regimen successfully elicited visceral obesity, hypertriglyceridemia, insulin resistance, and high blood pressure. The upregulation of de novo lipogenesis in the liver of the sucrose water-treated rats was demonstrated by an increased activity of enzymes, mRNA levels of lipogenic proteins, and nuclear levels of SREBP-1c and ChREBP. Moreover, in the sucrose water-treated rats, protein levels of PTP-1B were significantly increased in liver and skeletal muscle but decreased in adipose tissue. Conclusion: The susceptibility of Wistar rats to sucrose water-induced MS is associated with the transactivation of SREBP-1c and ChREBP in the liver, and PTP-1B is involved in the upregulation of de novo lipogenesis in the liver and the pathology of systemic insulin resistance in rats with MS chronically induced by drinking sucrose water.
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