No abstract

Oxidative stress is a cardinal manifestation of various intestinal disorders. However, very little knowledge is available on the intestine's inherent defense mechanisms against free radicals. This study was designed to determine the protein expression, subcellular localization and oxidative stress response of paraoxonase 2 (PON2), a member of a powerful antioxidant family in human and rat intestine. Biochemical and ultrastructural experiments all showed a substantial expression of PON2 in human and rat intestine. Western blot analysis disclosed higher levels of PON2 in the jejunum than in the duodenum, ileum, and colon. Cell fractionation revealed a predominant PON2 association with microsomes and lysosomes in the human jejunum, which differed from that in rats. PON2 was detected in the intestine as early as week 15 of gestation and was significantly increased by week 20. Iron ascorbate-mediated lipid peroxidation induced a marked decrease in PON2 expression in intestinal specimens coincidental to an abundant rise in malondialdehyde (MDA). On the other hand, preincubation with potent antioxidants, such as butylated hydroxytoluene, Trolox, and N-acetylcysteine, prevented iron-ascorbate-generating PON2 reduction in parallel with MDA suppression. Finally, the preincubation of permeabilized Caco-2 cells with purified PON2 led to a protection against iron-ascorbate-induced lipid peroxidation. These observations demonstrate that the human intestine is preferentially endowed with a marked PON2 expression compared with the rat intestine and this expression shows a developmental and intracellular pattern of distribution. Furthermore, our observations suggest PON2 protective effects against prooxidant stimuli in the small intestine.

No abstract

Hepatocyte nuclear factor 4␣ (HNF4␣) is a nuclear transcription factor mainly expressed in the liver, intestine, kidney, and pancreas. Many of its hepatic and pancreatic functions have been described, but limited information is available on its role in the gastrointestinal tract. The objectives of this study were to evaluate the anti-inflammatory and antioxidant functions of

Insulin resistance and type 2 diabetes (T2D) are characterized by hyperlipidemia. The aim of the present study was to elucidate whether T2D contributes to abnormal cholesterol (CHOL) homeostasis. Experiments were carried out in the small intestine and liver of Psammomys obesus, a model of nutritionally induced T2D. Our results show that diabetic animals exhibited a lower intestinal CHOL uptake, which was associated with a decrease in 1) the gene and protein expression of Niemann-Pick C1 like 1 that plays a pivotal role in CHOL incorporation in the enterocytes; and 2) mRNA of ATP-binding cassette transporters (ABC)A1 that mediates CHOL efflux from intestinal cells to apolipoprotein A-I and high-density lipoprotein. No changes were observed in the other intestinal transporters scavenger receptor-class B type I (SR-BI) and annexin 2. On the other hand, in diabetic animals, a significant mRNA decrease was noticed in intestinal ABCG5 and ABCG8 responsible for the secretion of absorbed CHOL back into the lumen. Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein receptor was raised, along with a significant down-regulation in jejunal 3-hydroxy-3-methylglutaryl-coenzyme A reductase in P. obesus with T2D. Finally, among the transcription factors tested, only an increase in liver X receptors alpha and a decrease in peroxisome proliferator-activated receptors delta/beta mRNAs were detected in the intestine. In the liver, there was 1) an augmentation in the protein mass of Niemann-Pick C1 like 1, SR-BI, and annexin 2; 2) an up-regulation of SR-BI mRNA; 3) a fall in ABCG8 protein content as well as in ABCG5 and ABCA1 mRNA; and 4) an augmentation in liver X receptors alpha and peroxisome proliferator-activated receptors beta/delta mRNA, together with a drop in sterol regulatory element binding protein-2 protein. Our findings show that the development in P. obesus with T2D modifies the whole intraenterocyte and hepatocyte machinery responsible for CHOL homeostasis.

Previously, we reported that a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, has immunomodulatory and anti-inflammatory properties. MPM consumption leads to a considerable reduction in the cytokine and chemokine production (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6), thus lowering chronic inflammation or metaflammation. Inhibition of metaflammation should provide positive impact, particularly in the context of dyslipidemia, insulin resistance, and hypertension. In this study, we investigated whether short-term MPM supplementation ameliorates those features of metabolic syndrome (MetS). The ability of MPM to potentially regulate triglyceride level, cholesterol level, blood glucose level, and hypertension was evaluated in different animal models. MPM lowers triglyceride level by 37% (P < .05) in a poloxamer 407 dyslipidemia-induced rat model. It also reduces total cholesterol by 18% (P < .05) and low-density lipoprotein-cholesterol level by 32% (P < .05) and raises high-density lipoprotein-cholesterol level by 17% (P < .01) in Syrian Golden hamsters fed a high fat/high cholesterol diet for 2 weeks. MPM reestablishes the fasting glucose insulin ratio index to normal levels (P = .07) in this latter model and lowers the plasma glucose level area under the curve (-10%, P = .09) in fructose-fed rats after 2 weeks of treatment. In spontaneously hypertensive rats, MPM-treated animals showed a reduction of SBP by at least 13% (P < .05) for 4 weeks. Results from this study suggest that MPM is a functional ingredient with beneficial effects on lipid metabolism, blood glucose control, and hypertension that might contribute to the management of MetS and thus reducing the risk of cardiovascular diseases.