@article{racine_iglesias-carres_herring_wieland_ellsworth_tessem_ferruzzi_kay_neilson_2024, title={The high-fat diet and low-dose streptozotocin type-2 diabetes model induces hyperinsulinemia and insulin resistance in male but not female C57BL/6J mice}, volume={131}, ISSN={["1879-0739"]}, DOI={10.1016/j.nutres.2024.09.008}, abstractNote={Translation of preclinical findings on the efficacy of dietary interventions for metabolic disease to human clinical studies is challenging due to the predominant use of male rodents in animal research. Our objective was to evaluate a combined high-fat (HF) diet and low-dose streptozotocin (STZ) model for induction of type-2 diabetes (T2D) in male and female C57BL/6J mice. We hypothesized that T2D biomarkers would differ significantly between sexes. Mice were administered either a low-fat (LF) diet (10% kcal from fat), or HF diet (60% kcal from fat) + STZ injections (30 mg/kg/d for 3 days). Both sexes gained weight and developed impaired postprandial oral glucose tolerance on the HF+STZ treatment compared to LF. Only male mice on HF + STZ developed fasting hyperglycemia, fasting hyperinsulinemia and insulin resistance, suggesting that the underlying causes of postprandial hyperglycemia differed between sexes. Principal component analysis of measures such as body weights, glucose and insulin concentrations indicated metabolic derangement for males only on HF+STZ treatment, while LF group males and both groups of females significantly overlapped. Based on our data, we accept our hypothesis that the combined high-fat diet and low-dose STZ model for T2D phenotypes differs significantly in its effect on mice based on sex. The HF diet + low-dose STZ model is not useful for studying insulin resistance in females. Other models are needed to model T2D, and study the effects of dietary interventions in this disease, in females. Sexual dimorphism remains a significant challenge for both preclinical and clinical research.}, journal={NUTRITION RESEARCH}, author={Racine, Kathryn C. and Iglesias-Carres, Lisard and Herring, Jacob A. and Wieland, Kristopher L. and Ellsworth, Peter N. and Tessem, Jeffery S. and Ferruzzi, Mario G. and Kay, Colin D. and Neilson, Andrew P.}, year={2024}, month={Nov}, pages={135–146} }
 @article{iglesias-carres_racine_chadwick_nunn_kalambur_neilson_ferruzzi_2023, title={Mechanism of off-color formation in potato chips fried in oil systems containing ascorbic acid as a stabilizer}, volume={179}, ISSN={["1096-1127"]}, DOI={10.1016/j.lwt.2023.114682}, abstractNote={The use of alternative, green antioxidant (AOX) systems is demanded by consumers. Natural AOX systems pose significant challenges. For example, in frying applications, these AOX can negatively alter potato chip color, one of the most important traits in consumer selection. We evaluated the role of natural AOX systems containing ascorbic acid, tocopherols, and other antioxidants in amino acid-related undesirable color formation in fried potato chips. Results indicated that both oil phase AOX and potato factors are critical to generation of off-color formation in fried potato chips through Maillard type reactions. Ascorbic acid solubilization in oil and migration to the chip surface play key roles in observed off-color formation. However, multiple complex reactions may be responsible for color development, which may involve food matrix components. Contributions of AOX other than ascorbic acid appear minimal. Nevertheless, some browning can occur regardless of the presence of ascorbic acid. Color formation through glutamine occurred in the absence of ascorbic acid, but its presence greatly exacerbates color generation, while color generation via asparagine is barely modulated by ascorbic acid. AOX and free amino acid concentrations, temperature, and moisture are critical factors for controlling undesirable color formation during frying with natural oil AOX systems.}, journal={LWT-FOOD SCIENCE AND TECHNOLOGY}, author={Iglesias-Carres, Lisard and Racine, Kathryn C. and Chadwick, Sydney and Nunn, Candace and Kalambur, Sathya B. and Neilson, Andrew P. and Ferruzzi, Mario G.}, year={2023}, month={Apr} }
 @article{racine_iglesias-carres_herring_ferruzzi_kay_tessem_neilson_2022, title={Cocoa extract exerts sex-specific anti-diabetic effects in an aggressive type-2 diabetes model: A pilot study}, volume={626}, ISSN={["1090-2104"]}, DOI={10.1016/j.bbrc.2022.08.018}, abstractNote={Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ (ob/ob) and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Acute cocoa reduced fasting hyperglycemia in females, but not males, after 2 weeks. Chronic cocoa supplementation (6-10 weeks) ameliorated hyperinsulinemia in males and worsened hyperlipidemia and hyperinsulinemia in females, yet also preserved and enhanced beta cell survival in females. The underlying mechanisms of these differences warrant further study. If sex differences are apparent in subsequent preclinical studies, clinical studies will be warranted to establish whether these differences are relevant in humans. Sex differences may need to be considered when designing human dietary interventions for T2D.}, journal={BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, author={Racine, Kathryn C. and Iglesias-Carres, Lisard and Herring, Jacob A. and Ferruzzi, Mario G. and Kay, Colin D. and Tessem, Jeffery S. and Neilson, Andrew P.}, year={2022}, month={Oct}, pages={205–210} }
 @article{weikart_indukuri_racine_coleman_kovac_cockburn_hopfer_neilson_lambert_2022, title={Effect of processing on the anti-inflammatory efficacy of cocoa in a high fat diet-induced mouse model of obesity}, volume={109}, ISSN={["1873-4847"]}, DOI={10.1016/j.jnutbio.2022.109117}, abstractNote={Obesity causes inflammation which may lead to development of co-morbidities like cardiovascular diseases. Cocoa is a popular food ingredient that has been shown to mitigate obesity and inflammation in preclinical models. Cocoa typically undergoes fermentation and roasting prior to consumption, which can affect the polyphenol content in cocoa. The aim of this study was to compare the effect of fermentation and roasting protocols on the ability of cocoa to mitigate obesity, gut barrier dysfunction, and chronic inflammation in high fat (HF)-fed, obese C57BL/6J mice. We found that treatment of mice with 80 mg/g dietary cocoa powder for 8 weeks reduced rate of body weight gain in both male and female mice (46-57%), regardless of fermentation and roasting protocol. Colonic length was increased (11-24%) and gut permeability was reduced (48-79%) by cocoa supplementation. Analysis of the cecal microbiome showed that cocoa, regardless of fermentation and roasting protocol, reduced the ratio of Firmicutes to Bacteroidetes. Multivariate statistical analysis of markers of inflammation and body weight data showed sex differences in the effect of both the HF diet as well as cocoa supplementation. Based on this data there was strong protective efficacy from cocoa supplementation especially for the more processed cocoa samples. Overall, this study shows that anti-obesity and anti-inflammatory efficacy of cocoa is resilient to changes in polyphenol content and composition induced by fermentation or roasting. Further, this study shows that although cocoa has beneficial effects in both males and females, there are significant sex differences.}, journal={JOURNAL OF NUTRITIONAL BIOCHEMISTRY}, author={Weikart, Daphne K. and Indukuri, Vijaya V. and Racine, Kathryn C. and Coleman, Kiana M. and Kovac, Jasna and Cockburn, Darrell W. and Hopfer, Helene and Neilson, Andrew P. and Lambert, Joshua D.}, year={2022}, month={Nov} }
 @article{iglesias-carres_racine_neilson_2022, title={Phenolic-rich beverages reduce bacterial TMA formation in an ex vivo-in vitro colonic fermentation model}, ISSN={["2042-650X"]}, DOI={10.1039/d2fo01159j}, abstractNote={Upper tract gastrointestinal digestion unlocks the ability of cocoa and coffee bioactives to inhibit bacterial TMA formation.}, journal={FOOD & FUNCTION}, author={Iglesias-Carres, Lisard and Racine, Kathryn C. and Neilson, Andrew P.}, year={2022}, month={Jul} }
 @article{griffin_essenmacher_racine_iglesias-carres_tessem_smith_neilson_2021, title={Diet-induced obesity in genetically diverse collaborative cross mouse founder strains reveals diverse phenotype response and amelioration by quercetin treatment in 129S1/SvImJ, PWK/EiJ, CAST/PhJ, and WSB/EiJ mice}, volume={87}, ISSN={["1873-4847"]}, DOI={10.1016/j.jnutbio.2020.108521}, abstractNote={Significant evidence suggests protective effects of flavonoids against obesity in animal models, but these often do not translate to humans. One explanation for this disconnect is use of a few mouse strains (notably C57BL/6 J) in obesity studies. Obesity is a multifactorial disease. The underlying causes are not fully replicated by the high-fat C57BL/6 J model, despite phenotypic similarities. Furthermore, the impact of genetic factors on the activities of flavonoids is unknown. This study was designed to explore how diverse mouse strains respond to diet-induced obesity when fed a representative flavonoid. A subset of Collaborative Cross founder strains (males and females) were placed on dietary treatments (low-fat, high-fat, high-fat with quercetin, high-fat with quercetin and antibiotics) longitudinally. Diverse responses were observed across strains and sexes. Quercetin appeared to moderately blunt weight gain in male C57 and both sexes of 129S1/SvImJ mice, and slightly increased weight gain in female C57 mice. Surprisingly, quercetin dramatically blunted weight gain in male, but not female, PWK/PhJ mice. For female mice, quercetin blunted weight gain (relative to the high-fat phase) in CAST/PhJ, PWK/EiJ and WSB/EiJ mice compared to C57. Antibiotics did not generally result in loss of protective effects of quercetin. This highlights complex interactions between genetic factors, sex, obesity stimuli, and flavonoid intake, and the need to move away from single inbred mouse models to enhance translatability to diverse humans. These data justify use of genetically diverse Collaborative Cross and Diversity Outbred models which are emerging as invaluable tools in the field of personalized nutrition.}, journal={JOURNAL OF NUTRITIONAL BIOCHEMISTRY}, author={Griffin, Laura E. and Essenmacher, Lauren and Racine, Kathryn C. and Iglesias-Carres, Lisard and Tessem, Jeffery S. and Smith, Susan M. and Neilson, Andrew P.}, year={2021}, month={Jan} }
 @article{racine_lee_stewart_blakeslee_neilson_2019, title={Development of a rapid ultra performance hydrophilic interaction liquid chromatography tandem mass spectrometry method for procyanidins with enhanced ionization efficiency}, volume={1594}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2019.02.007}, abstractNote={Cocoa flavanols (catechins and procyanidins) can exist in various polymerization states and are commonly classified by their degree of polymerization (DP). There is increasing evidence that flavanols of distinct DP possess different biological activities, but separation and quantification of the higher DP procyanidins is challenging and has thus created the need for new methodologies that utilize advancements in columns and LC–MS/MS systems. An aqueous normal phase (hydrophilic interaction liquid chromatography, HILIC), UPLC method with post-column ESI adjuvant infusion was developed to reduce the total analysis time, increase peak separation, and increase detection specificity (compared to traditional fluorescence methods) by coupling with mass spectrometry detection. The total elution time was reduced from 70 to 90 min (typically used for normal phase and HILIC HPLC separation of procyanidins) down to 9 min by employing UPLC. Results indicate that by using a post-column 0.04 M ammonium formate infusion (5 μL/min), ionization of procyanidins was significantly enhanced. Lower limits of detection ranged from 3.19 × 10−2 to 4.56 pmol-on-column, and lower limits of quantification ranged from 2.79 × 10−2 to 1.17 × 102 pmol-on-column across compounds DP 1–9. This method builds upon the foundation set by existing analytical methods and employs new technologies to dramatically increase sample throughput and enhance detection limits and specificity, facilitating improved analysis for procyanidins.}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Racine, Kathryn C. and Lee, Andrew H. and Stewart, Amanda C. and Blakeslee, Kenneth W. and Neilson, Andrew P.}, year={2019}, month={Jun}, pages={54–64} }
 @article{racine_wiersema_griffin_essenmacher_lee_hopfer_lambert_stewart_neilson_2019, title={Flavanol Polymerization Is a Superior Predictor of alpha-Glucosidase Inhibitory Activity Compared to Flavanol or Total Polyphenol Concentrations in Cocoas Prepared by Variations in Controlled Fermentation and Roasting of the Same Raw Cocoa Beans}, volume={8}, ISSN={["2076-3921"]}, DOI={10.3390/antiox8120635}, abstractNote={Raw cocoa beans were processed to produce cocoa powders with different combinations of fermentation (unfermented, cool, or hot) and roasting (not roasted, cool, or hot). Cocoa powder extracts were characterized and assessed for α-glucosidase inhibitory activity in vitro. Cocoa processing (fermentation/roasting) contributed to significant losses of native flavanols. All of the treatments dose-dependently inhibited α-glucosidase activity, with cool fermented/cool roasted powder exhibiting the greatest potency (IC50: 68.09 µg/mL), when compared to acarbose (IC50: 133.22 µg/mL). A strong negative correlation was observed between flavanol mDP and IC50, suggesting flavanol polymerization as a marker of enhanced α-glucosidase inhibition in cocoa. Our data demonstrate that cocoa powders are potent inhibitors of α-glucosidase. Significant reductions in the total polyphenol and flavanol concentrations induced by processing do not necessarily dictate a reduced capacity for α-glucosidase inhibition, but rather these steps can enhance cocoa bioactivity. Non-traditional compositional markers may be better predictors of enzyme inhibitory activity than cocoa native flavanols.}, number={12}, journal={ANTIOXIDANTS}, author={Racine, Kathryn C. and Wiersema, Brian D. and Griffin, Laura E. and Essenmacher, Lauren A. and Lee, Andrew H. and Hopfer, Helene and Lambert, Joshua D. and Stewart, Amanda C. and Neilson, Andrew P.}, year={2019}, month={Dec} }
 @article{griffin_fausnacht_tuzo_addington_racine_zhang_hughes_england_bruno_sean f. o'keefe_et al._2019, title={Flavanol supplementation protects against obesity-associated increases in systemic interleukin-6 levels without inhibiting body mass gain in mice fed a high-fat diet}, volume={66}, ISSN={["0271-5317"]}, DOI={10.1016/j.nutres.2019.03.011}, abstractNote={Weight gain and obesity are associated with increased levels of proinflammatory cytokines. Studies have demonstrated the ability of dietary flavanols to reduce the severity of metabolic derangements due to high-fat (HF) feeding. The degree of polymerization of the flavanols appears to play a role in determining the extent of these protective effects. This study evaluated the preventative effects of grape seed and pine bark flavanol supplementation, with significantly different flavanol degree of polymerization, in the context of an HF diet. For 13 weeks, mice were given 35 mg/kg body weight per day grape seed or pine bark as part of an HF diet and compared to mice fed a low-fat diet and control HF diet. All flavanol-supplemented groups and the HF control incurred significantly higher weight gain compared to the lean control, and the grape seed group gained significantly more weight than the HF control. Increased weight gain of treatment groups was likely caused by hyperphagia. Despite lack of improvements to weight gain and glycemic control, it was observed that all flavanol treatment groups were able to significantly reduce interleukin-6 compared to HF control. The grape seed group, which gained the most weight overall, also exhibited the lowest levels of interleukin-6 compared to other groups. Overall, low-dose flavanol extract supplementation, regardless of mean degrees of polymerization, blunted cytokine production despite increased weight gain. This obesity-independent effect suggests flavanols may be used as complementary interventions to ameliorate increased inflammatory tone in the contexts of obesity and diabetes. Furthermore, flavanol-induced hyperphagia may have use for attenuation of cachexia.}, journal={NUTRITION RESEARCH}, author={Griffin, Laura E. and Fausnacht, Dane W. and Tuzo, Jessica L. and Addington, Adele K. and Racine, Kathryn C. and Zhang, Haiyan and Hughes, Michael D. and England, Kathryn M. and Bruno, Richard S. and Sean F. O'Keefe and et al.}, year={2019}, month={Jun}, pages={32–47} }