@article{milhem_hamilton_skates_wilson_johanningsmeier_komarnytsky_2024, title={Biomarkers of Metabolic Adaptation to High Dietary Fats in a Mouse Model of Obesity Resistance}, volume={14}, ISSN={["2218-1989"]}, url={https://doi.org/10.3390/metabo14010069}, DOI={10.3390/metabo14010069}, abstractNote={Obesity-resistant (non-responder, NR) phenotypes that exhibit reduced susceptibility to developing obesity despite being exposed to high dietary fat are crucial in exploring the metabolic responses that protect against obesity. Although several efforts have been made to study them in mice and humans, the individual protective mechanisms are poorly understood. In this exploratory study, we used a polygenic C57BL/6J mouse model of diet-induced obesity to show that NR mice developed healthier fat/lean body mass ratios (0.43 ± 0.05) versus the obesity-prone (super-responder, SR) phenotypes (0.69 ± 0.07, p < 0.0001) by upregulating gene expression networks that promote the accumulation of type 2a, fast-twitch, oxidative muscle tissues. This was achieved in part by a metabolic adaptation in the form of blood glucose sparing, thus aggravating glucose tolerance. Resistance to obesity in NR mice was associated with 4.9-fold upregulated mitoferrin 1 (Slc25a37), an essential mitochondrial iron importer. SR mice also showed fecal volatile metabolite signatures of enhanced short-chain fatty acid metabolism, including increases in detrimental methyl formate and ethyl propionate, and these effects were reversed in NR mice. Continued research into obesity-resistant phenotypes can offer valuable insights into the underlying mechanisms of obesity and metabolic health, potentially leading to more personalized and effective approaches for managing weight and related health issues.}, number={1}, journal={METABOLITES}, author={Milhem, Fadia and Hamilton, Leah M. and Skates, Emily and Wilson, Mickey and Johanningsmeier, Suzanne D. and Komarnytsky, Slavko}, year={2024}, month={Jan} }
 @article{surzenko_bastidas_reid_curaba_zhang_bostan_wilson_dominique_roberson_ignacio_et al._2024, title={Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract}, volume={38}, ISSN={["1530-6860"]}, DOI={10.1096/fj.202301859R}, abstractNote={Abstract}, number={3}, journal={FASEB JOURNAL}, author={Surzenko, Natalia and Bastidas, Johana and Reid, Robert W. and Curaba, Julien and Zhang, Wei and Bostan, Hamed and Wilson, Mickey and Dominique, Ashley and Roberson, Julia and Ignacio, Glicerio and et al.}, year={2024}, month={Feb} }
 @article{milhem_skates_wilson_komarnytsky_2024, title={Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism}, volume={16}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu16010171}, DOI={10.3390/nu16010171}, abstractNote={Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.}, number={1}, journal={NUTRIENTS}, author={Milhem, Fadia and Skates, Emily and Wilson, Mickey and Komarnytsky, Slavko}, year={2024}, month={Jan} }
 @article{wilson_konda_heidt_rathinasabapathy_desai_komarnytsky_2021, title={Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model}, volume={22}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms22031032}, DOI={10.3390/ijms22031032}, abstractNote={Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.}, number={3}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, publisher={MDPI AG}, author={Wilson, Mickey and Konda, Veera and Heidt, Kathryn and Rathinasabapathy, Thirumurugan and Desai, Anuradha and Komarnytsky, Slavko}, year={2021}, month={Feb} }
 @article{skates_overall_dezego_wilson_esposito_lila_komarnytsky_2018, title={Berries containing anthocyanins with enhanced methylation profiles are more effective at ameliorating high fat diet-induced metabolic damage}, volume={111}, ISSN={["1873-6351"]}, url={https://doi.org/10.1016/j.fct.2017.11.032}, DOI={10.1016/j.fct.2017.11.032}, abstractNote={Driven by the need for alternative whole food options to manage metabolic syndrome, multiple dietary interventions are suggested to achieve a better control of metabolic risk factors and molecular networks that regulate cellular energy metabolism. It is generally accepted that anthocyanin-rich diets are beneficial for maintaining healthy body weight, improving glucose and lipid metabolism, and determining inflammatory status of key metabolic tissues. However, anthocyanins are a structurally diverse group of phenolic compounds and their individual contributions to improving metabolic health are not clear. In this study, we show that consumption of berries containing anthocyanins with enhanced methylation profiles (malvidin and petunidin) is more effective at reducing high fat diet-induced metabolic damage in the C57BL/6 mouse model of polygenic obesity. Blueberries and Concord grapes (57% and 33% anthocyanins as malvidin, petunidin, or peonidin, respectively) improved body composition through individual significant effects on energy expenditure and increased activity. Methylated anthocyanins are also more effective at enhancing mitochondrial respiration and dissipation of the mitochondrial proton gradient (proton leak) in adipose tissue, thus counteracting mitochondrial dysfunction associated with metabolic stress. Together, these results provide direct proof of the higher protective potential of methylated anthocyanins against the metabolic consequences of chronic exposure to calorie-dense foods.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, publisher={Elsevier BV}, author={Skates, Emily and Overall, John and DeZego, Katelyn and Wilson, Mickey and Esposito, Debora and Lila, Mary Ann and Komarnytsky, Slavko}, year={2018}, month={Jan}, pages={445–453} }
 @article{wagner_de gezelle_robertson_robertson_wilson_komarnytsky_2017, title={Antibacterial activity of medicinal plants from The Physicians of Myddvai, a 14th century Welsh medical manuscript}, volume={203}, ISSN={["1872-7573"]}, DOI={10.1016/j.jep.2017.03.039}, abstractNote={Antimicrobial drug resistance is a growing threat to global public health. Historical records and herbal texts relating to traditional Celtic medicine indicate an extensive pharmacopeia of plants for treating infections likely caused by microbes. However, a major barrier for successful integration of these remedies into mainstream practice is the current lack of accurate interpretation and scientific validation. We investigated the flora of the Isle of Arran, Scotland, via in situ targeted screening of 83 out of 138 plants identified in Meddygion Myddvai (a 14th century Welsh manuscript) to treat conditions related to microbial infections, and an additional 18 plants from modern ethnobotanical knowledge on the island (Scottish School of Herbal Medicine). In a follow-up proof-of-concept study, bioassay-guided fractionation was performed to identify bioactive constituents from two high scoring hits that inhibited Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacterial growth. 67 historical plants (80.7%) and 14 modern plants (77.8%) were found to have detectable levels of antimicrobial activity when tested using Mobile Discovery kits, with human saliva as a source of bacteria for screening. Sabinene, a natural bicyclic monoterpene from juniper “berries” (Juniperus communis L.) and alliin, a natural sulfoxide from garlic cloves (Allium sativum L.), were isolated and confirmed as primary antibacterial leads. Using historical medical sources such as those associated with traditional Celtic medicine to guide rigorous, evidence-based scientific investigation, provides additional leads for new and alternative bioactive molecules for combating bacterial diseases.}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, publisher={Elsevier BV}, author={Wagner, Charles Stephen and De Gezelle, Jillian and Robertson, Maureen and Robertson, Keith and Wilson, Mickey and Komarnytsky, Slavko}, year={2017}, month={May}, pages={171–181} }
 @article{overall_bonney_wilson_beermann_grace_esposito_lila_komarnytsky_2017, title={Metabolic Effects of Berries with Structurally Diverse Anthocyanins}, volume={18}, ISSN={["1422-0067"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85013078281&partnerID=MN8TOARS}, DOI={10.3390/ijms18020422}, abstractNote={Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.}, number={2}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Overall, John and Bonney, Sierra A. and Wilson, Mickey and Beermann, Arnold and Grace, Mary H. and Esposito, Debora and Lila, Mary Ann and Komarnytsky, Slavko}, year={2017}, month={Feb} }
 @article{esposito_damsud_wilson_grace_strauch_li_lila_komarnytsky_2015, title={Black Currant Anthocyanins Attenuate Weight Gain and Improve Glucose Metabolism in Diet-Induced Obese Mice with Intact, but Not Disrupted, Gut Microbiome}, volume={63}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84937064835&partnerID=MN8TOARS}, DOI={10.1021/acs.jafc.5b00963}, abstractNote={Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 μg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.}, number={27}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Esposito, Debora and Damsud, Thanakorn and Wilson, Mickey and Grace, Mary H. and Strauch, Renee and Li, Xu and Lila, Mary Ann and Komarnytsky, Slavko}, year={2015}, month={Jul}, pages={6172–6180} }