▼ β-carotene is a prominent human dietary carotenoid known for its provitamin A and antioxidant properties. In addition to these functions, eccentric cleavage of β-carotene at double bonds on the polyene chain other than the 15-15’ central double bond by autooxidation or the cytosolic enzyme β,β-carotene 9’,10’-oxygenase (BCO2) produces β-apocarotenoids of varying chain lengths that could have important biological roles. Long chain β-apocarotenoids share some structural characteristics similar to natural and synthetic ligands of peroxisome proliferator-activated receptor alpha (PPARα), a member of the steroid/retinoid nuclear receptor family. PPARα is known to have a vital role in lipid utilization, lipoprotein metabolism, and inflammatory responses. Therefore, we hypothesized that β-apocarotenoids can regulate gene expression by activating PPARα. Transactivation assays were performed using the COS-1 cell line transfected with PPARα nuclear receptor vector and treated with β-cyclogeranic acid (BCA), β-cyclocitral (BCL), β-ionylideneacetaldehyde (BIA), β-ionylideneacetic acid (BIAA), β-apo-13’-carotenone (C13 ketone), β-apo-8’-carotenal (CAL)/ carotenoic acid (CA), β-apo-12’-CAL/CA, or β-apo-14’-CAL/CA. The synthetic fibrate GW0742 was used as a positive control. We found that cells treated with BCL, β-apo-8’-CAL/CA, BIA, BIAA, β-apo-12’-CAL, and β-apo-14’-CAL did not activate PPARα. Administration of BCA, β-apo-12’-CA, C13 ketone, and β-apo-14’-CA to the cells resulted increased PPARα activity suggesting these β-apocarotenoids may function as PPARα agonists in vitro. Advisors/Committee Members: Harrison, Earl.

Advisors/Committee Members: Redick, Sharon S.

▼ As obesity rates continue to rise in America, so do obesity-linked disorders such as metabolic syndrome, cardiovascular disease and type 2 diabetes (T2DM). Older women are especially susceptible to these diseases because of hormonal changes after menopause. New research has shown the omega-6 polyunsaturated fatty acids, linoleic acid (LA), to be effective in attenuating metabolic syndrome symptoms. Despite this, public health messages continue to ignore LA and focus on omega-3 fatty acids, resulting in a good understanding of the health benefits of omega-3 fatty acids but confusion or lack of information about omega-6 fatty acids. New health messages are needed to inform the American public and especially postmenopausal women about LA. In order to effectively do so, a mental model should first be created to understand the women's current thoughts and beliefs about dietary fats and oils and the decisions they make regarding selection and use. The objective of this pilot study was to determine what women were currently consuming, to use the Risk Information Seeking and Processing model to frame the examination of women's current knowledge and information sufficiency with regards to dietary fats and oil products and their link to health, and, working within the human behavioral framework of the Theory of Planned Behavior, to determine the women's perceived behavioral control with regards to consuming healthy fats and oils. Twenty-one postmenopausal women with T2DM were recruited to participate in four focus groups and to complete a dietary fat and oil food frequency questionnaire that was developed and tested by the research team. Of the dietary fats and oil products that the women thought of as healthy, those that were high in omega-3 fatty acid and monounsaturated fatty acids were identified as major themes. The major themes for the women's consumption showed that the women tended to consume products that they had identified as healthy with only a few products that they viewed as unhealthy. In addition, all of the focus groups indicated that they would like to learn more information about healthy dietary fats and oil products. Taste, confusion/lack of information, and cost were most mentioned as major barriers to consuming healthy fats and oils with only a minor mention of a facilitator that promoted consumption. However, with the exception of cost, it was a major theme that the women felt that they had the power or personal means to overcome or diminish the impact of the barriers. It is promising that the women felt, for the most part, in control of their decision to consume healthy dietary fat and oils. While it is clear that current fat and oil health messages are being heard and acted upon by this sample of women, there evidence of information insufficiency about omega-6 fatty acids, and specifically LA. Future studies should validate these preliminary findings through use of survey data and with a larger sample. Advisors/Committee Members: Medeiros, Lydia.

▼ Vitamin A and its metabolites, retinoic acid (RA) and retinal, regulate multiple life-sustaining processes including vision, haematopoiesis, skeletal growth, fertility (male and female), embryogenesis, epithelial cell integrity against infections, and immunity. Deficiency in dietary vitamin A in animals leads to severe malfunction of the intestinal enzymes associated with mucosal immunity and decreased immunoglobulin A (IgA) production, or impaired IgA function. In HIV-infected children, supplementation with vitamin A decreases diarrhea and mortality. At present, the mechanisms by which vitamin A exerts its immune function remain poorly understood. Recent studies in animals supplemented with the vitamin A metabolite RA showed increases in IgA levels in mice. RA is generated from retinaldehyde by the aldehyde dehydrogenase-1 family of enzymes (Aldh1) that is comprised of three members: Aldh1A1, A2, and A3. Aldh1A1 is the major cytosolic enzyme involved in RA production. However, the role of Aldh1A1 in the regulation of IgA production has not been investigated. We hypothesize that Aldh1A1 affects immunoglobulin production in mice. We studied the effect of Aldh1A1 on IgA production in Aldh1A1-/- and WT mice on either a normal chow diet or a high-fat diet. Enzyme-linked immunosorbent assay (ELISA) was used to measure IgA and IgG levels in the plasma, spleen, and feces. Western blot was used to estimate IgA heavy chain and light kappa and lambda chains in spleen. Using ELISA, we demonstrated that IgA levels in plasma were significantly higher (292%) in Aldh1A1-/- (n=12) than WT (n=8) mice on regular chow. Plasma IgG levels were moderately higher in Aldh1A1-/- (127%) than in WT. Next we examined whether Aldh1A1 deficiency influences immunoglobulin production in major sites of immunoglobulin production by B cells. We found several abnormalities in the spleen of Aldh1A1 deficient mice. Aldh1A1-/- spleens were enlarged 120% as compared to WT mice. There were higher levels of spleen IgA (162%) in Aldh1A1-/- than in WT with a higher expression of light IgA kappa chains. Spleens had (307%) higher IgG levels in Aldh1A1-/- than WT mice. Fecal samples were used to investigate the effects of Aldh1A1 on immunoglobulin production at mucosal sites. Fecal IgA levels were the same in both groups. Significantly higher amounts of fecal IgG (4000%) were found in Aldh1A1-/- as compared to WT mice. A high fat diet appeared to additional influence immunoglobulin production. The Aldh1A1 dependent changes in immunoglobulin production were augmented by a high-fat diet. In high fat diet fed animals, plasma had 575% and 741% higher levels of IgA and IgG in Aldh1A1-/- than WT respectively. Spleens had (297%) higher IgG levels in Aldh1A1-/- mice as compared to WT. Both plasma and spleens expressed higher protein levels of light kappa chain in Aldh1A1 -/- than in WT mice on a high-fat diet. Our data reveal that the Aldh1A1 enzyme suppresses immunoglobulin A and G production and plays a significant role in the regulation of immunoglobulins light chain levels in response to diet. Advisors/Committee Members: Harrison, Earl H.

Advisors/Committee Members: Cremer, Marion L.

▼ Obesity is a problem affecting people around much of the world. Intake of soy may decrease tissue lipid accumulation and adipose tissue mass. We aimed to determine the effect of fermented soy product on weight gain and adiposity in growing male C57Bl/6 mice. Eight week old mice were put in a Casein diet, Soy diet, or Fermented Soy diet (FSoy) group for 17 weeks. Half of the mice fed the Casein diet were switched to the FSoy diet at 8 weeks (CtoFSoy). The FSoy reduced weight gain and adiposity compared to the Soy diet and the Casein diet. At 16 weeks, fasting glucose from the FSoy was significantly lower than the Casein diet or Soy diet. In an insulin tolerance test (ITT), glucose lowering was more dramatic from the FSoy compared to the Soy or Casein diet. Fasting insulin was significantly lower in the FSoy and Soy diet compared to the Casein, and the FSoy group was significantly lower than the Soy group. Serum leptin was significantly reduced from the FSoy and Soy diet compared to the Casein diet. The FSoy diet peroxisome proliferator activated receptor gamma (PPAR-γ) mRNA was significantly lowered compared to the Soy diet. FSoy reduced adipose mass, plasma insulin and glucose, serum leptin, insulin tolerance, and adipose tissue responses in fatty acid-binding protein-4 (FABP4), hormone-sensitive lipase (HSL) and F4/80 gene transcription. These data suggest that the beneficial weight and insulin responsiveness observed in the C57Bl/6 mice from the FSoy study diet are largely due to PPAR-γ-independent mechanisms, and may, in part, be due to PPAR-α-dependent mechanisms. Advisors/Committee Members: Belury, Martha.