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Showing papers by "Thomas M. Badger published in 2007"


Journal ArticleDOI
TL;DR: Overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via total enteral nutrition suggests maternal obesity at conception leads to fetal programming of offspring, which could result in obesity in later life.

138 citations


Journal ArticleDOI
TL;DR: In this article, the authors used electrospray ionization mass spectrometry (ESI−MS) with both positive and negative ion modes to identify vitamin E and γ-oryzanol components in rice bran and germ.
Abstract: Rice bran is a rich natural source of vitamin E and γ-oryzanol, which have been extensively studied and reported to possess important health-promoting properties. However, commercial rice bran is a mixture of rice bran and germ, and profiles of vitamin E and γ-oryzanol components in these two different materials are less well-studied. In the current study, vitamin E and γ-oryzanol components in rice bran and germ were analyzed by liquid chromatography/mass spectrometry/mass spectrometry. The components were identified by electrospray ionization mass spectrometry (ESI−MS) with both positive- and negative-ion modes. Both deprotonated molecular ion [M − H]- and protonated molecular ion [M + H]+ found as the base peaks in spectra of vitamin E components made ESI−MS a valuable analytic method in detecting vitamin E compounds, especially when they were at very low levels in samples. Ultraviolet absorption was used for quantification of vitamin E and γ-oryzanol components. While the level of vitamin E in rice ge...

89 citations


Journal ArticleDOI
TL;DR: This article contains the proceedings of a symposium at the 2006 ISBRA meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger, about the effect of long-term ethanol consumption on liver injury and repair.
Abstract: This article contains the proceedings of a symposium at the 2006 ISBRA meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of long-term ethanol consumption on liver injury and repair, by Jack R. Wands; (2) Alcohol-induced insulin resistance in liver: potential roles in regulation of ADH expression, ethanol clearance, and alcoholic liver disease, by Thomas M. Badger; (3) Chronic gestational exposure to ethanol causes brain insulin and insulin-like growth factor resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 signaling in muscle: a mechanism underlying alcoholic myopathy, by Charles H. Lang; (5) The role of reduced plasma estradiol and impaired estrogen signaling in alcohol-induced bone loss, by Martin J. Ronis; and (6) Short-term influence of alcohol on appetite-regulating hormones in man, by Jan Calissendorff.

68 citations


Journal Article
TL;DR: Research using the TEN system has demonstrated that alcohol-induced fetal growth retardation is potentiated by undernutrition in part via impaired alcohol metabolism and clearance, which is an important determinant of fetal alcohol toxicity.
Abstract: Metabolism of alcohol (i.e., ethanol) is regulated by genetic and environmental factors as well as physiologic state. For a given alcohol intake, the rate of alcohol clearance, which ultimately determines tissue ethanol concentrations, may be the most significant risk factor for many of the detrimental effects of alcohol. Faster ethanol clearance would help minimize target tissue concentrations, and in pregnant women, mitigate fetal alcohol exposure. Much remains to be known about the effects of the altered endocrine milieu of pregnancy on alcohol metabolism and clearance in the mother. Research has shown that among pregnant rats allowed unrestricted access to alcohol and those fed alcohol containing liquid diets under experimental conditions via a feeding tube (total enteral nutrition [TEN]), urine ethanol concentrations (and thus blood and tissue ethanol concentrations) are lower in pregnant rats compared with non-pregnant females given the same dose of ethanol. Maternal nutritional status also is an important determinant of fetal alcohol toxicity. Research using the TEN system has demonstrated that alcohol-induced fetal growth retardation is potentiated by undernutrition in part via impaired alcohol metabolism and clearance.

61 citations


Journal ArticleDOI
TL;DR: Evidence is provided in rats that low-dose alcohol intake enhances hepatic insulin signaling by suppressing p55gamma at the posttranscriptional level, leading to the increased association of the phosphatidylinositol 3-kinase catalytic subunit with insulin receptor substrate-1, and alcohol exerts biphasic actions on insulin signaling.
Abstract: Routine consumption of alcohol at low doses is associated with decreased risk of acquiring type 2 diabetes, whereas chronic and excessive alcohol consumption increases the risk. Although there is good epidemiologic evidence for these biphasic effects, careful validation of these effects on insulin signaling has not been reported, nor have biological mechanisms underlying these biphasic effects been proposed. In this study, we provide evidence in rats that low-dose alcohol intake (4 g/kg·d) enhances hepatic insulin signaling by suppressing p55γ (a phosphatidylinositol 3-kinase regulatory subunit isoform) at the posttranscriptional level, leading to the increased association of the phosphatidylinositol 3-kinase catalytic subunit (p110) with insulin receptor substrate-1 (P < 0.05) and subsequent activation of downstream effectors such as Akt, glycogen synthase kinase 3β, and nuclear sterol regulatory element binding protein (SREBP)-1. These results, combined with our previous data (confirmed in the present s...

43 citations


Journal ArticleDOI
TL;DR: It is concluded that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model.

30 citations


Journal ArticleDOI
TL;DR: It is concluded that undernutrition does not exacerbate alcoholic steatohepatitis despite additional oxidative stress produced by an increased induction of CYP2E1 and CYP4A1 and enhanced ethanol-induced cellular proliferation, perhaps as a result of enhanced PPAR-alpha signaling, may contribute to an increased risk of hepatocellular carcinoma in undernourished alcoholics.
Abstract: To assess the relative contributions of undernutrition and ethanol (EtOH) exposure to alcohol-induced hepatotoxicity, female Sprague-Dawley rats were intragastrically infused liquid diets containin...

29 citations


Journal ArticleDOI
TL;DR: The data suggest that postlactational anabolic rebuilding is influenced by EtOH consumption and may affect the long‐term risk of osteopenia.
Abstract: EtOH consumption significantly impaired anabolic rebuilding of bone after lactation. Lower BMD and BMC in EtOH-fed rats were associated with decreased bone formation in the proximal tibia, increased proportion of adipocytes, and increased expression of TNF-α. EtOH-induced skeletal deficits were prevented by treatment with either NAC or sTNFR1. These data suggest that postlactational anabolic rebuilding is influenced by EtOH consumption and may affect the long-term risk of osteopenia. Introduction: Despite significant loss of bone during lactation, BMD is restored by a powerful anabolic rebuilding process after weaning. A significant number of women resume alcohol consumption after weaning their offspring from breast feeding. The objectives of this study were to examine the consequences of chronic ethanol (EtOH) consumption on the postlactational rebuilding process and to investigate the underlying mechanisms by which EtOH mediates its detrimental effects. Materials and Methods: Female Sprague-Dawley rats (n = 7–9 per group) were fed EtOH-containing diets (13 g/kg/d) for 1, 2, or 4 wk after weaning of their offspring. Skeletal parameters in the proximal tibia were examined using pQCT, μCT, and histomorphometric techniques, and interventional studies were performed on the mechanistic roles of EtOH-induced oxidative stress and TNF-α. Results and Conclusions: EtOH consumption completely abolished the anabolic bone rebuilding that occurred after lactation. Decreased BMD and BMC were associated with decreased bone formation and not with increased osteoclast activity. Furthermore, EtOH-fed rats showed greater proportion of fat volume/bone volume and expression of adipocyte-specific genes. EtOH-induced skeletal effects were mitigated by the dietary antioxidant, N-acetyl cysteine or by blocking TNF-α signaling. These data suggest EtOH consumption in the period immediately postweaning may significantly impair the mother's skeletal health and lead to long-term osteopenia.

29 citations


Journal ArticleDOI
TL;DR: Results indicate an effect of dietary protein type during pregnancy on colon tumor multiplicity and colon tissue gene expression, and serum IGF-I and testosterone in progeny rats as later adults.
Abstract: We examined effects of dietary soy protein isolate (SPI) or genistein (GEN; soy isoflavone) during pregnancy on development of colon cancer in male progeny Sprague‐Dawley rats. Fourgroupsofratswereused:alifetimecasein-fedgroup(CAS; control diet), a lifetime SPI-fed group (positive control for protectiveeffectofdietoncoloncarcinogenesis),agroupwhose dams received SPI only during pregnancy and CAS thereafter (SPI/CAS), and a group whose dams received CASCGEN only during pregnancyand CAS thereafter (GEN/CAS). At 47 and 55 days of age, male progeny were administered the intestinal carcinogen azoxymethane (AOM). Tumors, endocrine status, and colon gene expression were evaluated at 20 week post-AOM. The SPI group had 47% decreased colon tumor incidence compared with the CAS group (P!0.05), whereas SPI/CAS, GEN/CAS, and CAS groups did not differ in this regard. Maternal-only SPI increased the percentage of animals bearing multiple colon tumors (P!0.05), an effect not mimicked by GEN. Serum insulin and leptin concentrations weredecreasedbylifetimeSPI(P!0 . 05),whereasserumIGF-I was elevated in the SPI/CAS group (P!0.05). The SPI/CAS group had reduced serum testosterone levels (P!0.05) and exhibited a tendency for increasedmucosal expression of IGF-I receptorandglucosetransporter-1mRNAs.Resultsindicatean effect of dietary protein type during pregnancyon colon tumor multiplicity and colon tissue gene expression, and serum IGF-I and testosterone in progeny rats as later adults.

25 citations


Journal ArticleDOI
TL;DR: Feeding a casein-based formula to newborn piglets may compromise the development of GALT and systemic immune system, and the neonatal piglet model may be used to identify the effects of dietary factors on the developed neonatal immune system.
Abstract: Background: Controversy exists concerning diet-induced changes to gut epithelia and immunocytes that occur during weaning. Furthermore, studies on dietary effects on the development of the neonatal immune system, especially gut-associated lymphoid tissue (GALT), are lacking. Objective: The purpose of this study was to investigate growth and development, intestinal morphology, and GALT immune maturation in sow-reared littermates in comparison with early-weaned piglets fed a casein-based liquid diet. Method: Piglets were breast fed by the sow or were weaned at 48 h to a casein-based diet (formula) that provided the amount of nutrient requirements recommended by the National Research Council. Results: Gross physical appearance and visual inspection of the gastrointestinal tract and other organs at necropsy revealed normal organogenesis in both cohorts. On postnatal day 21, body weight, liver and kidney weight relative to body weight, small intestine length, and weight-to-length ratio were greater in formula-fed piglets as compared with sow-reared piglets (p Conclusions: Feeding a casein-based formula to newborn piglets may compromise the development of GALT and systemic immune system. Further, the neonatal piglet model may be used to identify the effects of dietary factors on the development of the neonatal immune system.

20 citations


Journal ArticleDOI
TL;DR: The findings suggest that the cancer preventive effect of soy-based diets is mediated in part by reduction in AhR protein level posttranslationally, which reduces procarcinogen-induced CYP1A1 induction and metabolic activation.
Abstract: Consumption of a soy diet has been found to reduce cancer incidence in animals and is associated with reduced cancer risk in humans. In this study, the effect of consuming soy protein isolate (SPI) on the aryl hydrocarbon receptor (AhR)-mediated signaling pathway was investigated. Female Sprague-Dawley rats were fed AIN-93G diets with (+) or without (-) SPI-bound phytochemicals or casein (CAS) protein and gavaged orally with 7,12-dimethylbenz[a]anthracene (DM BA) or sesame oil. We found reduced (P 20 d. Experiments in which SPI + -fed rats were weaned to CAS diets demonstrated that AhR reduction by SPI + is not imprinted metabolically. To determine the molecular mechanisms of SPI + -mediated AhR reduction, an ex vivo model was developed using FGC-4 cells treated with serum from CAS- or SPI + -fed rats. SPI + serum treatment of FGC-4 cells reduced AhR expression and DMBA-induced CYP1A1 expression (P < 0.05). The reduction in AhR expression was in part due to the shorter half-life of AhR protein. Our findings suggest that the cancer preventive effect of soy-based diets is mediated in part by reduction in AhR protein level posttranslationally, which reduces procarcinogen-induced CYP1A1 induction and metabolic activation.

Journal ArticleDOI
TL;DR: Examining the brain event-related potentials of healthy infants receiving breast milk or milk-based formula recorded in response to consonant vowel syllables presented in an oddball paradigm suggests advantages for BF infants in the development and processing of language stimuli during the first 6 months of life.
Abstract: The purpose of this investigation was to determine if processing of language stimuli during the first half year of life in breast-fed infants differs from that of formula-fed infants. This question was addressed by examining the brain event-related potentials of healthy infants receiving breast milk (n = 15) or milk-based formula (n = 18) recorded in response to consonant vowel syllables presented in an oddball paradigm. The same infants were studied when they were 3-months and 6-months-old. The two groups were comparable on several measures relating to biological and home environment variables previously reported to influence development, including gestation period, birth weight, mother's IQ, and family socioeconomic status, and did not differ in weight or mental or motor development at the times of the visits. In general, ERP response features previously documented in studies of syllable processing in 3–6-month-old infants were observed in this study, including positive components at ∼ 190 msec (P1), ∼ ...

Journal ArticleDOI
TL;DR: Whether agouti signaling protein (ASIP) levels in A vy /a or a/a livers are associated with hepatocyte proliferation as a possible factor in promotion of hepatocellular tumor formation is ascertained and ASIP levels were found to be ~100-fold higher in yellow than in pseudoagouti or black mice.
Abstract: Enhanced linear growth, hyperplasia, and tumorigenesis are well-known characteristics of “viable yellow” agouti Avy/- mice (Wolff GL, Roberts DW, Mountjoy KG. Physiol Genomics 1:151–163, 1999); however, the functional basis for this aspect of the phenotype is unknown. In the present study, we ascertained whether agouti signaling protein (ASIP) levels in Avy/a or a/a livers are associated with hepatocyte proliferation as a possible factor in promotion of hepatocellular tumor formation. Proliferating cell nuclear antigen (PCNA) assays and quantitative real-time reverse transcriptase polymerase chain reaction assays were performed on liver samples from mottled yellow Avy/a, pseudoagouti Avy/a, and black a/a VY mice to determine mitotic indices and expression levels of Avy and a in relation to the expression level of the housekeeping gene hprt. We found that ASIP levels were ~100-fold higher in yellow than in pseudoagouti or black mice and that the proportion of PCNA-positive hepatocytes was greater (P < 0.00...

Journal ArticleDOI
TL;DR: Data suggest that the processing of the present speech stimuli is not affected by the investigated diets in the early infancy, and the between-stimulus differences in frontal P200 amplitudes were positively correlated with the behavioral scores of Bayley Index of Infant Development.
Abstract: Effects of breast milk and milk formula supplemented with docosahexaenoic acid and arachidonic acid on speech processing were investigated by recording event-related potentials (ERPs) to synthesized /pa/ and /ba/ (oddball paradigm, 80%:20%) at 3 and 6 months of age. Behavioral assessment was also obtained. A major positive component (P200) was elicited by both types of sounds. It had a maximal scalp distribution in the fronto-central areas in both groups of infants. The mean latencies did not differ between the groups or between the stimulus types. However, the latencies decreased across age in both groups. The mean P200 amplitude in the formula-fed infants was lower than that in the breast-fed infants, but the difference was not significant. The between-stimulus differences in frontal P200 amplitudes were positively correlated with the behavioral scores of Bayley Index of Infant Development. These data suggest that the processing of the present speech stimuli is not affected by the investigated diets in the early infancy.


Journal ArticleDOI
TL;DR: A "two-hit" model for NASH exists in which development of steatosis constitutes the "first hit" and sensitizes the liver to potential "second hits" resulting in NASH.
Abstract: A "two-hit" model for NASH exists in which development of steatosis constitutes the "first hit" and sensitizes the liver to potential "second hits" resulting in NASH. Oxidative stress is possibly a...