The Journal of Nutritional Biochemistry

2010-03-01

Antiobesity mechanisms of action of conjugated linoleic acid

2009-12-02

Abstract: Conjugated linoleic acid (CLA), a family of fatty acids found in beef, dairy foods and dietary supplements, reduces adiposity in several animal models of obesity and some human studies. However, the isomer-specific antiobesity mechanisms of action of CLA are unclear, and its use in humans is controversial. This review will summarize in vivo and in vitro findings from the literature regarding potential mechanisms by which CLA reduces adiposity, including its impact on (a) energy metabolism, (b) adipogenesis, (c) inflammation, (d) lipid metabolism and (e) apoptosis.

Gender affects liver desaturase expression in a rat model of n−3 fatty acid repletion

2009-01-21

Abstract: Dietary n−3 polyunsaturated fatty acids (PUFA) are major components of cell membranes and have beneficial effects on human health. Docosahexaenoic acid (DHA; 22:6n−3) is the most biologically important n−3 PUFA and can be synthesized from its dietary essential precursor, α-linolenic acid (ALA; 18:3n−3). Gender differences in the efficiency of DHA bioconversion have been reported, but underlying molecular mechanisms are unknown. We compared the capacity for DHA synthesis from ALA and the expression of related enzymes in the liver and cerebral cortex between male and female rats. Wistar rats, born with a low-DHA status, were supplied with a suboptimal amount of ALA from weaning to 8 weeks of age. Fatty acid composition was determined by gas chromatography, the mRNA expression of different genes involved in PUFA metabolism was determined by RT-PCR (low-density array) and the expression of proteins was determined by Western blot analysis. At 8 weeks, DHA content was higher (+20 to +40%) in each phospholipid class of female livers compared to male livers. The “Δ4,” Δ5 and Δ6 desaturation indexes were 1.2–3 times higher in females than in males. The mRNA expression of Δ5- and Δ6-desaturase genes was 3.8 and 2.5 times greater, respectively, and the Δ5-desaturase protein was higher in female livers (+50%). No gender difference was observed in the cerebral cortex. We conclude that female rats replete their DHA status more readily than males, probably due to a higher expression of liver desaturases. Our results support the hypothesis on hormonal regulation of PUFA metabolism, which should be taken into account for specific nutritional recommendations.

Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction

Krista A. Varady, Candice A. Allister, Donald J. Roohk, Marc K. Hellerstein — 2009-02-06

Abstract: Calorie restriction (CR) and alternate-day fasting (ADF) beneficially affect several aspects of adipose tissue physiology, but direct comparisons between regimens have yet to be performed. The present study evaluated the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and examined the kinetic mechanisms that underlie changes in fat distribution. Thirty female C57BL/6J mice were randomized to one of five groups for 4 weeks: (a) CR-25% (25% energy restriction daily), (b) ADF-75% (75% restriction on fast day), (c) ADF-85% (85% restriction on fast day), (d) ADF-100% (100% restriction on fast day) and (e) control (ad libitum fed). Body weights of the CR mice were lower than that of the ADF and control groups posttreatment. After 4 weeks of diet, the proportion of visceral fat decreased (P<.001) and the proportion of subcutaneous fat increased (P<.001) similarly in ADF and CR animals. Adiponectin increased (P<.05) by 62–86% in the ADF groups and by 69% in the CR group. Triglyceride (TG) synthesis and de novo lipogenesis were augmented (P<.05) in the subcutaneous fat pad of ADF and CR animals, relative to control. No differences in net lipolysis were observed, resulting in greater TG accumulation in the subcutaneous fat pad, with a shift in the ratio of TG between depots. These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR.

Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cells

2009-02-06

Abstract: Oxidative stress is widely recognized as an important mediator of apoptosis in liver cells and plays a pivotal role in the pathogenesis of several diseases. Cocoa flavonoids have shown a powerful antioxidant activity providing protection against oxidation and helping prevent oxidative stress-related diseases. However, the molecular mechanisms responsible for this protection are not fully understood. Thus, in this study we investigated the protective effect of a cocoa polyphenolic extract (CPE) against tert-butyl hydroperoxide (t-BOOH)-induced apoptosis and the molecular mechanisms involved in this process. Incubation of HepG2 cells with t-BOOH induced apoptosis as evidenced by caspase-3 activation. This effect was accompanied by increased reactive oxygen species formation and by transient activation of the extracellular regulated kinases (ERKs) as well as sustained activation of the c-Jun N-terminal kinases (JNKs). On the contrary, pretreatment of HepG2 cells with CPE prevented apoptosis through the reduction of reactive oxygen species generation and the modulation of the apoptotic pathways activated by t-BOOH. CPE treatment also activated survival signaling proteins, such as protein kinase B (AKT) and ERKs, and increased the activities of two antioxidant enzymes, glutathione peroxidase (GPx) and glutathione reductase (GR). ERK's implication on GPx and GR induction and the protective effect of CPE against t-BOOH-induced oxidative stress and apoptosis were confirmed through experiments with selective inhibitors. These findings suggest that CPE is an effective inductor of GPx and GR activities via ERK activation and that this up-regulation seems to be required to attenuate t-BOOH-induced injury.

Inhibitory effects of γ-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells

2009-02-06

Abstract: Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially γ-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by γ-tocotrienol were explored. The results showed the inhibitory effects of γ-tocotrienol at doses of 15, 30, 45 and 60 μmol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the γ-tocotrienol treatments. SGC-7901 cell attachment decreased in the γ-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that γ-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with γ-tocotrienol for 48 h (P<.05). γ-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of γ-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.

Developmental changes in glycolipids and synchronized expression of nutrient transporters in the mouse small intestine

2009-03-09

Abstract: Small intestinal epithelial cells are rich in characteristic glycosphingolipids (GSLs) that are composed of phytosphingosine and α-hydroxy fatty acid, but the physiological roles of GSLs in the small intestine remain unclear. Here, we report the developmental changes in GSL composition in the mouse small intestine (duodenum through ileum) and their relationship with the temporal mRNA expression of nutrient transporters. Up to 2 weeks after birth, the major GSLs were hexosylceramide (HexCer), GM3, GM1 and GD1a. After 2 weeks of age, HexCer and asialo GM1 became the major GSLs. The ceramide moiety of both HexCer and asialo GM1 was composed mainly of phytosphingosine and α-hydroxy fatty acid, from birth through adulthood. Immunohistochemically, GM1 localized in the cytoplasm, and asialo GM1 localized exclusively in the apical microvillous membrane of small intestinal epithelial cells. The shift from sialylated GSLs to asialo GM1 was achieved by the combinational and tissue-specific transcriptional down-regulation of GM3 synthase and GM1-β-galactosidase at around 2 weeks of age. The temporal mRNA expression of various nutrient transporters also showed significant changes at around 2 weeks of age, including the up-regulation of the sodium/glucose cotransporter and the oligopeptide transporter, as well as the down-regulation of amino acid transporters. These synchronized changes in the mRNA expression of nutrient transporters with GSL composition during suckling-to-weanling transition suggest the contributions of GSLs to morphologic and functional development in the membrane of mouse small intestinal epithelial cells.

Vitamin A deficiency alters rat lung alveolar basement membrane Reversibility by retinoic acid

2009-03-09

Abstract: Vitamin A is essential for lung development and pulmonary cell differentiation and its deficiency results in alterations of lung structure and function. Basement membranes (BMs) are also involved in those processes, and retinoic acid, the main biologically active form of vitamin A, influences the expression of extracellular matrix macromolecules. Therefore, we have analyzed the ultrastructure and collagen content of lung alveolar BM in growing rats deficient in vitamin A and the recovering effect of all-trans retinoic acid. Male weanling pups were fed a retinol-adequate or -deficient diet until they were 60 days old. A group of vitamin A-deficient pups were recovered by daily intraperitoneal injections of all-trans retinoic acid for 10 days. Alveolar BM in vitamin A-deficient rats doubled its thickness and contained irregularly scattered collagen fibrils. Immunocytochemistry revealed that these fibrils were composed of collagen I. Total content of both collagen I protein and its mRNA was greater in vitamin-deficient lungs. In agreement with the greater size of the BM the amount of collagen IV was also increased. Proinflammatory cytokines, IL-1α, IL-1β and TNF-α, did not change, but myeloperoxidase and TGF-β1 were increased. Treatment of vitamin A-deficient rats with retinoic acid reversed all the alterations, but the BM thickness recovered only partially. Retinoic acid recovering activity occurred in the presence of increasing oxidative stress. In conclusion, vitamin A deficiency results in alterations of the structure and composition of the alveolar BM which are probably mediated by TGF-β1 and reverted by retinoic acid. These alterations could contribute to the impairment of lung function and predispose to pulmonary disease.

Zinc supplementation partially prevents renal pathological changes in diabetic rats

2009-04-15

Abstract: We have demonstrated that Zn supplementation mediated up-regulation of cardiac metallothionein (MT) as a potent antioxidant prevented the development of diabetic cardiomyopathy. The present study was undertaken to test whether induction of renal MT synthesis by Zn supplementation protects the kidney from diabetes-induced damage. Streptozotocin-induced diabetic rats were treated with and without Zn supplementation at 5 mg/kg in drinking water for 3 months. Diabetic renal damage was detected by examining renal pathological alterations and 24-h urinary protein levels. Three-month Zn supplementation immediately after the onset of diabetes, partially but significantly, prevented the kidney from diabetes-induced increases in 24-h urinary proteins and pathological alterations. Diabetes-induced renal oxidative damage, inflammation and up-regulated expression of profibrosis mediator connective tissue growth factor (CTGF) were also markedly attenuated by Zn supplementation, along with significant increases in Zn levels concomitant with MT expression in renal tubular cells. Direct exposure of renal tubular (HK11) cells to high levels of glucose (HG) induced CTGF up-regulation predominantly through ERK (extracellular signal-regulated kinase)1/2-dependent, and partially through p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Pretreatment of HK11 cells with Zn or cadmium induced MT expression and also significantly suppressed HG-induced CTGF expression. These results provide the first evidence for Zn supplementation to attenuate diabetes-induced renal pathological changes, likely through prevention of hyperglycemia-induced CTGF expression by Zn-induced MT in renal tubular cells.

Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation

2009-04-15

Abstract: Caseinphosphopeptides (CPPs) are considered as mineral carriers because of their ability to bind and solubilize calcium ions, with the possible role, yet to be definitely assessed, of improving calcium absorption at the intestinal level. Previous works demonstrated that CPPs improve calcium uptake, with increasing intracellular calcium concentration, by human differentiated tumor HT-29 cells, and that this effect correlates with the supramolecular structure of CPPs in the presence of calcium ions. The aim of the present study was to establish whether the CPP effect on calcium uptake is specific for HT-29 cells and depends on the differentiated state of the cells. To this purpose, HT-29 and Caco2 cells, two models of intestinal cells, were differentiated following appropriate protocols, including treatment with 1,25-(OH)2 vitamin D3. The CPP-dependent intracellular calcium rises were monitored at the single-cell level through fura2-fluorescence assays, and cell differentiation was assessed by biochemical and morphological methods. Results clearly showed that the ability to take up extracellular calcium ions under CPP stimulation is exhibited by both HT-29 and Caco2 cells, but only upon cell differentiation. This evidence adds novel support to the notion that CPPs favour calcium absorption, thus possibly acting as cellular bio-modulators and carrying a nutraceutical potential.

The Journal of Nutritional Biochemistry

Contents

Antiobesity mechanisms of action of conjugated linoleic acid

Gender affects liver desaturase expression in a rat model of n−3 fatty acid repletion

Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction

Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cells

Inhibitory effects of γ-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells

Developmental changes in glycolipids and synchronized expression of nutrient transporters in the mouse small intestine

Vitamin A deficiency alters rat lung alveolar basement membrane Reversibility by retinoic acid

Zinc supplementation partially prevents renal pathological changes in diabetic rats

Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation