Rocio Zapata Bustos
- Assistant Research Professor, Medicine
- (520) 626-8727
- Arizona Health Sciences Center, Rm. 6121
- Tucson, AZ 85724
- rocioz@arizona.edu
Biography
Dr. Zapata is a Research Assistant Professor in the College of Medicine at University of Arizona since November 2018. She joined the University of Arizona in May 2016 as a postdoctoral fellow. Prior to joining the University of Arizona, Dr. Zapata was a postdoctoral fellow in the Center for Metabolic and Vascular Biology (CMVB) at the Arizona State University (ASU) and Mayo Clinic at Scottsdale, Arizona. Dr. Zapata completed her master and Ph.D. degrees at the Instituto Potosino de Investigación Ciencia y Tecnología (IPICYT) in San Luis Potosi, Mexico.
Dr. Zapata works under the guidance and mentorship of Dr. Lawrence Mandarino and oversees the activities of the Clinical Studies Team housed in the Clinical & Translational Sciences Research Center (CATS).
Degrees
- Ph.D. Molecular Biology
- Instituto Potosino de Investigacion Cientifica y Tecnologica (IPICYT), San Luis Potosi, San Luis Potosi, Mexico
- “Antidiabetic molecular mechanisms of plants used in the traditional medicine”
- M.S. Molecular Biology
- Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), San Luis Potosi, San Luis Potosi, Mexico
- “Molecular mechanisms of the hypoglycemic effect of plants traditionally used as antidiabetics”
- B.S. Pharmaco-biological chemistry
- Autonomous University of San Luis Potosí, UASLP, San Luis Potosi, San Luis Potosi, Mexico
- “Preadipocyte cellular proliferation and differentiation in L15 medium”
Work Experience
- University of Arizona, Tucson, Arizona (2016 - 2019)
- Mayo/ASU Center for Metabolic and Vascular Biology (2014 - 2016)
Awards
- Award to 2nd place in poster presentation
- Arizona Physiological Society., Fall 2017
- Doctoral Fellowship
- CONACYT (Consejo Nacional de Ciencia y Tecnología, National Council of Science and Technology), Fall 2009
- Award “Alfredo Sánchez Marroquín 2009” in the Undergraduate category for “Senior Thesis”.
- Mexican Society of Biotechnology and Bioengineering., Summer 2009
- Award “Dr. Miguel Otero y Arce 2009” in Basic Research category.
- Ministry of Health of San Luis Potosí., Spring 2009
- Honorable Mention at the “First National Contest in Basic Sciences and Creativity”
- Universidad Iberoamericana, Summer 2008 (Award Nominee)
- Award “Dr. Miguel Otero y Arce 2008” First place in Basic Research category.
- Ministry of Health of San Luis Potosí., Spring 2008
- Masters Fellowship
- CONACYT (Consejo Nacional de Ciencia y Tecnología, National Council of Science and Technology), Fall 2007
Licensure & Certification
- Bachelor in Science, Autonomous University of San Luis Potosí, UASLP (2008)
Interests
Research
Dr. Zapata’s research interest are to study the molecular mechanisms underlying mitochondrial dysfunction and the role of mitochondria in insulin resistance and metabolic inflexibility; as well as understanding the molecular mechanisms regulating exercise response and exercise resistance in patients with type 2 diabetes mellitus.
Courses
No activities entered.
Scholarly Contributions
Journals/Publications
- Mandarino, L. J., Willis, W. T., Funk, J. L., Langlais, P. R., Davidson, L., Galons, J., Coletta, D. K., & Zapata Bustos, R. (2023). Nonequilibrium thermodynamics and mitochondrial protein content predict insulin sensitivity and fuel selection during exercise in human skeletal muscle. Front Physiol.
- Mandarino, L. J., Willis, W. T., Funk, J. L., Luo, M., Kohler, L. N., Langlais, P. R., Coletta, D. K., Zapata Bustos, R., & Barakati, N. (2023). Fuel Selection in Skeletal Muscle Exercising at Low Intensity; Reliance on Carbohydrate in Very Sedentary Individuals. Metabolic Syndrome and Related Disorders.
- Mandarino, L. J., Willis, W. T., Funk, J. L., Luo, M., Kohler, L. N., Langlais, P. R., Coletta, D. K., Zapata Bustos, R., & Barakati, N. (2022). Fuel Selection in Skeletal Muscle Exercising at Low Intensity; Reliance on Carbohydrate in Very Sedentary Individuals. Metabolic Syndrome and Related Disorders.
- Zapata-bustos, R., Wu, L., Roust, L. R., Mandarino, L. J., Leon, A. D., Krentzel, J., Hamzaoui, Y., Garcia, L. A., Filippis, E. D., Day, S. E., Coletta, R. L., Coletta, D. K., & Campos, B. (2022). Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?. Metabolites, 12(3), 222. doi:10.3390/metabo12030222More infoSkeletal muscle is highly plastic and dynamically regulated by the body's physical demands. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to 8 weeks of supervised exercise training in volunteers with a range of insulin sensitivities. We studied 13 sedentary participants and performed euglycemic hyperinsulinemic clamps with basal vastus lateralis muscle biopsies and peak aerobic activity (VO2 peak) tests before and after training. We extracted DNA from the muscle biopsies and performed global methylation using Illumina's Methylation EPIC 850K BeadChip. Training significantly increased peak aerobic capacity and insulin-stimulated glucose disposal. Fasting serum insulin and insulin levels during the steady state of the clamp were significantly lower post-training. Insulin clearance rates during the clamp increased following the training. We identified 13 increased and 90 decreased differentially methylated cytosines (DMCs) in response to 8 weeks of training. Of the 13 increased DMCs, 2 were within the following genes, FSTL3, and RP11-624M8.1. Of the 90 decreased DMCs, 9 were within the genes CNGA1, FCGR2A, KIF21A, MEIS1, NT5DC1, OR4D1, PRPF4B, SLC26A7, and ZNF280C. Moreover, pathway analysis showed an enrichment in metabolic and actin-cytoskeleton pathways for the decreased DMCs, and for the increased DMCs, an enrichment in signal-dependent regulation of myogenesis, NOTCH2 activation and transmission, and SMAD2/3: SMAD4 transcriptional activity pathways. Our findings showed that 8 weeks of exercise training alters skeletal muscle DNA methylation of specific genes and pathways in people with varying degrees of insulin sensitivity.
- Bustos, R. Z., Langlais, P. R., Mandarino, L. J., Filippis, E. A., Grandjean, D., Luo, M., Coletta, D. K., & Finlayson, J. (2021). Altered Transcription Factor Expression Responses to Exercise in Insulin Resistance. Frontiers in Physiology. doi:10.3389/fphys.2021.649461More infoPurpose Insulin resistant muscle is resistant to gene expression changes induced by acute exercise. This study was undertaken to identify transcription factors that differentially respond to exercise in insulin resistance. Candidate transcription factors were identified from analysis of 5′-untranslated regions (5′-UTRs) of exercise responsive genes and from analysis of the 5′-UTRs of genes coding for proteins that differ in abundance in insulin resistance. Research Design and Methods Twenty participants took part in this study. Insulin sensitivity was assessed by an euglycemic clamp. Participants were matched for aerobic capacity and performed a single 48 min bout of exercise with sets at 70 and 90% of maximum heart rate. Muscle biopsies were obtained at resting conditions, 30 min and 24 h after exercise. Global proteomics analysis identified differentially abundant proteins in muscle. The 5′-UTRs of genes coding for significant proteins were subjected to transcription factor enrichment analysis to identify candidate transcription factors. Q-rt-PCR to determine expression of candidate transcription factors was performed on RNA from resting and post-exercise muscle biopsies; immunoblots quantified protein abundance. Results Proteins involved in mitochondrial function, protein targeting and translation, and metabolism were among those significantly different between lean and obese groups. Transcription factor enrichment analysis of genes coding for these proteins revealed new candidate transcription factors to be evaluated along the previously identified factors. Q-rt-PCR analysis of RNA and immunoblot analysis from pre- and post-exercise muscle biopsies revealed several transcription and growth factors that had altered responses to exercise in insulin resistant participants. A significant increase (EGR3 and CTGF) and decrease (RELA and ATF2) in the mRNA expression of transcription and growth factors was found after exercise in the lean group, but not in the obese participants. Conclusions These results confirm findings of an association between insulin sensitivity and transcription factor mRNA response to exercise and show that obesity also may be a sufficient prerequisite for exercise resistance. Analysis of the muscle proteome together with determination of effects of exercise on expression of transcription factors suggests that abnormal responses of transcription factors to exercise may be responsible for differences in protein abundances in insulin resistant muscle.
- Bustos, R. Z., Mandarino, L. J., Willis, W. T., Luo, M., Coletta, D. K., Funk, J. L., Langlais, P. R., Barakati, N., & Finlayson, J. (2021). Site-specific acetylation of adenine nucleotide translocase 1 at lysine 23 in human muscle. Analytical Biochemistry. doi:10.1016/j.ab.2021.114319More infoEvidence suggests acetylation of human adenine nucleotide translocase 1 (ANT1) at lysine 23 (Lys23) reduces binding of ADP. Lys23 contributes to the positive charge that facilitates this interaction. This study was undertaken to characterize ANT1 abundance and acetylation by a novel method using small amounts of human skeletal muscle biopsies. Lysates of whole muscle or mitochondria from the same tissue were prepared from needle biopsies of vastus lateralis muscle of healthy volunteers. Lysed proteins were resolved on gels, the section containing ANT1 (surrounding 30 Kd) was excised, digested with trypsin, spiked with labeled unacetylated and acetylated synthetic standard peptides and analyzed by mass spectrometry. Natural logarithm transformation of data linearized ion intensities over a 10-fold range of peptide mass. Coefficients of variation ranged from 7 to 30% for ANT1 abundance and Lys23 acetylation. In three volunteers, ANT1 content was 8.36 ± 0.33 nmol/g wet weight muscle and 0.64 ± 0.05 nmol/mg mitochondria, so mitochondrial content was 13.3 ± 2.4 mg mitochondria per gram muscle. Acetylation of Lys23 averaged 14.3 ± 4.2% and 4.87 ± 1.84% in whole muscle and mitochondria, respectively. This assay makes it possible to assess effects of acetylation on the function of ANT1 in human muscle. • Lysine acetylation of ANT1 alters the affinity of the protein for ADP. • A method to quantify lysine acetylation of human ANT1 in human muscle is presented. • The method also gives ANT1 content per mg mitochondrial protein.
- Bustos, R. Z., Willis, W. T., Mandarino, L. J., Ma, W., & Luo, M. (2021). Deletion of Von Willebrand A Domain Containing Protein (VWA8) raises activity of mitochondrial electron transport chain complexes in hepatocytes. Biochemistry and biophysics reports. doi:10.1016/j.bbrep.2021.100928
- Finlayson, J., Barakati, N., Langlais, P. R., Funk, J., Zapata Bustos, R., Coletta, D. K., Luo, M., Willis, W. T., & Mandarino, L. J. (2021). Site-specific acetylation of adenine nucleotide translocase 1 at lysine 23 in human muscle. Analytical biochemistry, 630, 114319.More infoEvidence suggests acetylation of human adenine nucleotide translocase 1 (ANT1) at lysine 23 (Lys23) reduces binding of ADP. Lys23 contributes to the positive charge that facilitates this interaction. This study was undertaken to characterize ANT1 abundance and acetylation by a novel method using small amounts of human skeletal muscle biopsies. Lysates of whole muscle or mitochondria from the same tissue were prepared from needle biopsies of vastus lateralis muscle of healthy volunteers. Lysed proteins were resolved on gels, the section containing ANT1 (surrounding 30 Kd) was excised, digested with trypsin, spiked with labeled unacetylated and acetylated synthetic standard peptides and analyzed by mass spectrometry. Natural logarithm transformation of data linearized ion intensities over a 10-fold range of peptide mass. Coefficients of variation ranged from 7 to 30% for ANT1 abundance and Lys23 acetylation. In three volunteers, ANT1 content was 8.36 ± 0.33 nmol/g wet weight muscle and 0.64 ± 0.05 nmol/mg mitochondria, so mitochondrial content was 13.3 ± 2.4 mg mitochondria per gram muscle. Acetylation of Lys23 averaged 14.3 ± 4.2% and 4.87 ± 1.84% in whole muscle and mitochondria, respectively. This assay makes it possible to assess effects of acetylation on the function of ANT1 in human muscle.
- Ma, W., Willis, W. T., Luo, M., Mandarino, L. J., & Zapata Bustos, R. (2021). Deletion of Von Willebrand A Domain Containing Protein (VWA8) Raises Activity of Mitochondrial Electron Transport Chain Complexes in Hepatocytes. Biochemical and Biophysical Research Communications. doi:doi: 10.1016/j.bbrep.2021.100928
- Mandarino, L. J., De Filippis, E. A., Grandjean, D., Luo, M., Coletta, D. K., Langlais, P. R., Finlayson, J., & Zapata Bustos, R. (2021). Altered Transcription Factor Expression Responses to Exercise in Insulin Resistance. Frontiers in Physiology.
- Mandarino, L. J., Willis, W. T., Luo, M., Coletta, D. K., Zapata Bustos, R., Funk, J. L., Langlais, P. R., Barakati, N., & Finlayson, J. (2021). Site-specific acetylation of adenine nucleotide translocase 1 at lysine 23 in human muscle. Analytical biochemistry, 630, 114319.More infoEvidence suggests acetylation of human adenine nucleotide translocase 1 (ANT1) at lysine 23 (Lys23) reduces binding of ADP. Lys23 contributes to the positive charge that facilitates this interaction. This study was undertaken to characterize ANT1 abundance and acetylation by a novel method using small amounts of human skeletal muscle biopsies. Lysates of whole muscle or mitochondria from the same tissue were prepared from needle biopsies of vastus lateralis muscle of healthy volunteers. Lysed proteins were resolved on gels, the section containing ANT1 (surrounding 30 Kd) was excised, digested with trypsin, spiked with labeled unacetylated and acetylated synthetic standard peptides and analyzed by mass spectrometry. Natural logarithm transformation of data linearized ion intensities over a 10-fold range of peptide mass. Coefficients of variation ranged from 7 to 30% for ANT1 abundance and Lys23 acetylation. In three volunteers, ANT1 content was 8.36 ± 0.33 nmol/g wet weight muscle and 0.64 ± 0.05 nmol/mg mitochondria, so mitochondrial content was 13.3 ± 2.4 mg mitochondria per gram muscle. Acetylation of Lys23 averaged 14.3 ± 4.2% and 4.87 ± 1.84% in whole muscle and mitochondria, respectively. This assay makes it possible to assess effects of acetylation on the function of ANT1 in human muscle.
- Zapata Bustos, R., Finlayson, J., Langlais, P. R., Coletta, D. K., Luo, M., Grandjean, D., De Filippis, E. A., & Mandarino, L. J. (2021). Altered Transcription Factor Expression Responses to Exercise in Insulin Resistance. Frontiers in Physiology.
- Zapata Bustos, R., Mandarino, L. J., Luo, M., Willis, W. T., & Ma, W. (2021). Deletion of Von Willebrand A Domain Containing Protein (VWA8) Raises Activity of Mitochondrial Electron Transport Chain Complexes in Hepatocytes. Biochemical and Biophysical Research Communications.
- Coletta, D. K., Bustos, R. Z., Mandarino, L. J., Langlais, P. R., Grandjean, D., Filippis, E. A., Coletta, D. K., & Bustos, R. Z. (2020). 166-OR: Lower Response of Connective Tissue Growth Factor (CTGF) to Exercise Characterizes Insulin Resistant Muscle. Diabetes, 69(Supplement_1). doi:10.2337/db20-166-orMore infoThis study was undertaken to identify transcription factors that differentially respond to exercise in insulin resistance. Candidate transcription factors were identified from analysis of 5’-untranslated regions (5’-UTRs) of exercise responsive genes and from analysis of the 5’-UTRs of genes coding for proteins that differ in abundance in insulin resistance. Muscle biopsies were obtained from lean and obese subjects before, 30 min and 240 h. after a single exercise bout. Insulin sensitivity was assessed through glucose clamps. Obese subjects (n=8) were insulin resistant compared to lean (n=12) (7.0 ± 0.95 vs. 11.3 ± 0.8 mg∙kg FFM-1∙min-1, P Disclosure R. Zapata Bustos: None. P.R. Langlais: None. D.K. Coletta: None. E.A. De Filippis: None. D. Grandjean: None. L. Mandarino: None. Funding National Institutes of Health (R01DK047936, DK066483, R01DK094013)
- Coletta, D. K., Bustos, R. Z., Mandarino, L. J., Leon, A. D., Lee, S., Krentzel, J. A., Garcia, L. A., Coletta, D. K., Campos, B., & Bustos, R. Z. (2020). 167-OR: Exercise Training Alters Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1 Alpha) DNA Methylation in Human Skeletal Muscle. Diabetes, 69(Supplement_1). doi:10.2337/db20-167-orMore infoExercise training improves insulin sensitivity in skeletal muscle and increases mitochondrial function. These improvements are due, in part, to an increase in expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha). The effect of exercise training on epigenetic factors, such as DNA methylation remains elusive. The aim of this study was to determine whether an 8-week exercise training alters DNA methylation of PGC-1 alpha. Fourteen participants (5M/9F; age 34.2±3.0 years) were studied before and after 8-weeks of supervised exercise training (60% of VO2peak for 20 minutes, 3 times per week; gradually increased to 70% of VO2peak for 45 minutes, 4 times per week). Euglycemic hyperinsulinemic clamps in combination with vastus lateralis muscle biopsies were obtained before and after the exercise training. Training increased peak aerobic capacity (VO2peak) from 31.9±1.0 to 36.5±1.4 ml∙min-1∙kg FFM-1 (P = 0.013) and improved insulin sensitivity from 7.0±2.1 to 9.2±2.3 ml·kg FFM−1·min−1. Genomic DNA was extracted and pyrosequencing methylation analysis was performed on CpG -816 and -783 bp upstream transcription start site (TSS). Methylation analysis revealed a significantly decreased methylation at CpG -816 bp following exercise (pre = 16.8±0.9 % versus post = 14.2±0.5 %, P = 0.035). For CpG -783 bp, methylation did not change following exercise (pre = 11±0.6 % versus post = 11.5±0.7 %, P = NS). Our results showed that exercise training improved insulin sensitivity and peak aerobic capacity. In addition, we provide evidence that exercise training alters PGC-1 alpha methylation at CpG -816 bp. We propose that the increased response of insulin action in muscle following exercise training is due, in part, to epigenetic modifications. Disclosure S. Lee: None. L. Garcia: None. A.D. Leon: None. R. Zapata Bustos: None. B. Campos: None. J.A. Krentzel: None. L. Mandarino: None. D.K. Coletta: None. Funding National Institutes of Health (R01DK094013)
- Willis, W. T., Miranda-Grandjean, D., Hudgens, J., Willis, E. A., Finlayson, J., De Filippis, E. A., Zapata Bustos, R., Langlais, P. R., Mielke, C., & Mandarino, L. J. (2018). Dominant and sensitive control of oxidative flux by the ATP-ADP carrier in human skeletal muscle mitochondria: Effect of lysine acetylation. Archives of biochemistry and biophysics, 647, 93-103.More infoThe adenine nucleotide translocase (ANT) of the mitochondrial inner membrane exchanges ADP for ATP. Mitochondria were isolated from human vastus lateralis muscle (n = 9). Carboxyatractyloside titration of O consumption rate (J) at clamped [ADP] of 21 μM gave ANT abundance of 0.97 ± 0.14 nmol ANT/mg and a flux control coefficient of 82% ± 6%. Flux control fell to 1% ± 1% at saturating (2 mM) [ADP]. The KmADP for J was 32.4 ± 1.8 μM. In terms of the free (-3) ADP anion this KmADP was 12.0 ± 0.7 μM. A novel luciferase-based assay for ATP production gave KmADP of 13.1 ± 1.9 μM in the absence of ATP competition. The free anion KmADP in this case was 2.0 ± 0.3 μM. Targeted proteomic analyses showed significant acetylation of ANT Lysine23 and that ANT1 was the most abundant isoform. Acetylation of Lysine23 correlated positively with KmADP, r = 0.74, P = 0.022. The findings underscore the central role played by ANT in the control of oxidative phosphorylation, particularly at the energy phosphate levels associated with low ATP demand. As predicted by molecular dynamic modeling, ANT Lysine23 acetylation decreased the apparent affinity of ADP for ANT binding.
- Bustos, R. Z., Mandarino, L. J., Willis, W. T., Stubblefield, T. M., Shi, C., Zhu, Y. X., Finlayson, J., Ma, W., Mengos, A., & Luo, M. (2017). Characterization of the novel protein KIAA0564 (Von Willebrand Domain-containing Protein 8). Biochemical and Biophysical Research Communications. doi:10.1016/j.bbrc.2017.04.067More infoThe VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564. Based on the observation, by similarity, that the protein encoded by KIAA0564 contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost unknown. The purpose of this study was to characterize the tissue distribution, cellular location, and function of VWA8. In mice VWA8 protein was mostly distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present as a long isoform and a shorter splice variant (VWA8a and VWA8b). VWA8 protein and mRNA were elevated in mouse liver in response to high fat feeding. Sequence analysis suggests that VWA8 has a mitochondrial targeting sequence and domains responsible for ATPase activity. VWA8 protein was targeted exclusively to mitochondria in mouse AML12 liver cells, and this was prevented by deletion of the targeting sequence. Moreover, the VWA8 short isoform overexpressed in insect cells using a baculovirus construct had in vitro ATPase activity. Deletion of the Walker A motif or Walker B motif in VWA8 mostly blocked ATPase activity, suggesting Walker A motif or Walker B motif are essential to the ATPase activity of VWA8. Finally, homology modeling suggested that VWA8 may have a structure most confidently similar to dynein motor proteins.
- Luo, M., Mengos, A. E., Ma, W., Finlayson, J., Bustos, R. Z., Xiao Zhu, Y., Shi, C. X., Stubblefield, T. M., Willis, W. T., & Mandarino, L. J. (2017). Characterization of the novel protein KIAA0564 (Von Willebrand Domain-containing Protein 8). Biochemical and biophysical research communications, 487(3), 545-551.More infoThe VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564. Based on the observation, by similarity, that the protein encoded by KIAA0564 contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost unknown. The purpose of this study was to characterize the tissue distribution, cellular location, and function of VWA8. In mice VWA8 protein was mostly distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present as a long isoform and a shorter splice variant (VWA8a and VWA8b). VWA8 protein and mRNA were elevated in mouse liver in response to high fat feeding. Sequence analysis suggests that VWA8 has a mitochondrial targeting sequence and domains responsible for ATPase activity. VWA8 protein was targeted exclusively to mitochondria in mouse AML12 liver cells, and this was prevented by deletion of the targeting sequence. Moreover, the VWA8 short isoform overexpressed in insect cells using a baculovirus construct had in vitro ATPase activity. Deletion of the Walker A motif or Walker B motif in VWA8 mostly blocked ATPase activity, suggesting Walker A motif or Walker B motif are essential to the ATPase activity of VWA8. Finally, homology modeling suggested that VWA8 may have a structure most confidently similar to dynein motor proteins.
- Zapata-Bustos, R., Alonso-Castro, A. J., Gómez-Sánchez, M., & Salazar-Olivo, L. A. (2014). Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway. Journal of ethnopharmacology, 152(3), 546-52.More infoIbervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).
- Alonso-Castro, A. J., Zapata-Bustos, R., Gómez-Espinoza, G., & Salazar-Olivo, L. A. (2012). Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway. Endocrinology, 153(11), 5222-30.More infoIsoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.
- Ortiz-Andrade, R., Cabañas-Wuan, A., Arana-Argáez, V. E., Alonso-Castro, A. J., Zapata-Bustos, R., Salazar-Olivo, L. A., Domínguez, F., Chávez, M., Carranza-Álvarez, C., & García-Carrancá, A. (2012). Antidiabetic effects of Justicia spicigera Schltdl (Acanthaceae). Journal of ethnopharmacology, 143(2), 455-62.More infoJusticia spicigera is a plant species used for the Teenak (Huesteca Potosina) and Mayan (Yucatan peninsula) indigenous for the empirical treatment of diabetes, infections and as stimulant.
- Alonso-Castro, A. J., Zapata-Bustos, R., Domínguez, F., García-Carrancá, A., & Salazar-Olivo, L. A. (2011). Magnolia dealbata Zucc and its active principles honokiol and magnolol stimulate glucose uptake in murine and human adipocytes using the insulin-signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology, 18(11), 926-33.More infoSome Magnolia (Magnoliaceae) species are used for the empirical treatment of diabetes mellitus, but the antidiabetic properties of Magnolia dealbata have not yet been experimentally validated. Here we report that an ethanolic extract of Magnolia dealbata seeds (MDE) and its active principles honokiol (HK) and magnolol (MG) induced the concentration-dependent 2-NBDG uptake in murine 3T3-F442A and human subcutaneous adipocytes. In insulin-sensitive adipocytes, MDE 50 μg/ml induced the 2-NBDG uptake by 30% respect to insulin, while HK and MG, 30 μM each, did it by 50% (murine) and 40% (human). The simultaneous application of HK and MG stimulated 2-NBDG uptake by 70% in hormone-sensitive cells, on which Magnolia preparations exerted synergic effects with insulin. In insulin-resistant adipocytes, MDE, HK and MG induced 2-NBDG uptake by 57%, 80% and 96% respect to Rosiglitazone (RGZ), whereas HK and MG simultaneously applied stimulated 2-NBDG uptake more efficiently than RGZ (120%) in both murine and human adipocytes. Inhibitors of the insulin-signaling pathway abolished the glucose uptake induced by Magnolia dealbata preparations, suggesting that their antidiabetic effects are mediated by this signaling pathway. In addition, MDE, HK and MG exerted only mild to moderate proadipogenic effects on 3T3-F442A and human preadipocytes, although the combined application of HK and MG markedly increased the lipid accumulation in both cell types. In summary, Magnolia dealbata and its active principles HK and MG stimulate glucose uptake in insulin-sensitive and insulin-resistant murine and human adipocytes using the insulin signaling pathway.
- Jacobo-Salcedo, M. d., Alonso-Castro, A. J., Salazar-Olivo, L. A., Carranza-Alvarez, C., González-Espíndola, L. A., Domínguez, F., Maciel-Torres, S. P., García-Lujan, C., González-Martínez, M. d., Gómez-Sánchez, M., Estrada-Castillón, E., Zapata-Bustos, R., Medellin-Milán, P., & García-Carrancá, A. (2011). Antimicrobial and cytotoxic effects of Mexican medicinal plants. Natural product communications, 6(12), 1925-8.More infoThe antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.
- Alonso-Castro, A. J., Zapata-Bustos, R., Romo-Yañez, J., Camarillo-Ledesma, P., Gómez-Sánchez, M., & Salazar-Olivo, L. A. (2010). The antidiabetic plants Tecoma stans (L.) Juss. ex Kunth (Bignoniaceae) and Teucrium cubense Jacq (Lamiaceae) induce the incorporation of glucose in insulin-sensitive and insulin-resistant murine and human adipocytes. Journal of ethnopharmacology, 127(1), 1-6.More infoTecoma stans (L.) Juss. ex Kunth (Bignoniaceae) and Teucrium cubense Jacq (Lamiaceae) are plants extensively used for the empirical treatment of diabetes mellitus, but their antidiabetic mechanisms remain to be clarified. In this study, the effect of aqueous extracts of Tecoma stans (TSE) and Teucrium cubense (TCE) on the glucose uptake in adipose cells was evaluated.
- Herrera-Herrera, M. L., Zapata-Bustos, R., & Salazar-Olivo, L. A. (2009). Simplified culture techniques for growth and differentiation of murine and human pre-adipocytes for translational applications. Cytotherapy, 11(1), 52-60.More infoAdipose tissue has become a promising source of adult stem cells. Looking for optimal culture conditions, we evaluated the ability of L15, a free-gas exchange culture medium, to support cell proliferation and adipogenesis of murine 3T3-F442A and human normal (HNPA) and lipoma-derived (HLPA) pre-adipocytes.
- Zapata-bustos, R., Romo-yanez, J., Salazar-olivo, L., & Alonso-castro, A. J. (2009). Opuntia leucotricha possesses insulin-like activities inducing glucose uptake in murine and human normal and diabetic-like adipocytes. Planta Medica, 75(09). doi:10.1055/s-0029-1234943
- Zapata-bustos, R., Romo-yanez, J., Salazar-olivo, L., & Alonso-castro, A. J. (2009). Teucrium cubense induces glucose-uptake in insulin-sensitive and insulin-resistant murine and human adipocytes. Planta Medica, 75(09). doi:10.1055/s-0029-1234942More infoWe investigated the anti-diabetic mechanisms of Teucrium cubense Jacq (Lamiaceae) assaying non-toxic concentrations of an aqueous extract of this plant (TE) on the 2-NBDglucose uptake [1] and adipogenesis [2] in 3T3-F442A murine and normal human subcutaneous adipocytes. In insulin-sensitive 3T3 adipocytes, TE stimulated the 2-NBDG uptake by 112% whereas in human adipocytes induced the 2-NBDG uptake by 54% respect to the 2-NBDG uptake stimulated by insulin. TE also induced 2-NBDG uptake in insulin-resistant murine and human adipocytes by 69% and 31% respectively. TE (70µg/mL) added to murine adipogenic medium increased 3T3 adipogenesis by 167% whereas added to human adipogenic medium induced human adipogenesis by 138%. Under non adipogenic conditions, TE only marginally increased adipogenesis by 13% in 3T3 preadipocytes and by 9% in human preadipose cells, suggesting that this preparation lacks of pro-adipogenic effects. Our results suggest that Teucrium cubense exerts its anti-diabetic effects stimulating glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes without affecting triglyceride accumulation. Acknowledgements: RZB and AJAC were endowed with graduate fellowships from CONACYT (211445 and 210841, respectively). AJAC also received special support from IPICYT (SA-157/2008). References: [1] Alonso-Castro, A.J., Salazar-Olivo, L.A. (2008). J. Ethnopharmacol. 118:252–256. [2] Ramirez-Zacarias, J.L. et al. (1992) Histochem. 97:493–497.
Presentations
- Mandarino, L. J., Grandjean, D. N., De Filippis, E. A., Coletta, D. K., Langlais, P. R., & Zapata Bustos, R. (2020, June). Lower Response of Connective Tissue Growth Factor (CTGF) to Exercise Characterizes Insulin Resistant Muscle. American Diabetes Association 80th scientific sessions. Chicago, IL: American Diabetes Association.More infoRocio Zapata-Bustos, Paul Langlais, Dawn Coletta, Elena A. De Filippis, Danielle Grandjean, Lawrence J. MandarinoLower Response of Connective Tissue Growth Factor (CTGF) to Exercise Characterizes Insulin Resistant Muscle
- Zapata Bustos, R. (2018, May). Evaluation of the exercise-induced transcriptional program regulation in lean and obese subjects. Endocrinology Journal Club Works in Progress. Tucson, Arizona: Department of Medicine, Division of Endocrinology, University of Arizona.More infoZapata-Bustos R. Evaluation of the exercise-induced transcriptional program regulation in lean and obese subjects. Department of Medicine, Division of Endocrinology, University of Arizona. Endocrinology Journal Club Works in Progress, May 08, 2018
- Zapata Bustos, R. (2017, February). Proteomic Analysis of the Vastus Lateralis from Lean and Obese Subjects: Evaluation of the Acetylome in Response to Exercise. Endocrinology Journal Club Works in Progress. Tucson, Arizona: Department of Medicine, Division of Endocrinology, University of Arizona..More infoZapata-Bustos R. Proteomic Analysis of the Vastus Lateralis from Lean and Obese Subjects: Evaluation of the Acetylome in Response to Exercise. Department of Medicine, Division of Endocrinology, University of Arizona. Endocrinology Journal Club Works in Progress, February 28, 2017
- Zapata Bustos, R. (2016, November). Proteomic Analysis of the Vastus Lateralis from Lean and Obese Subjects: Evaluation of the Acetylome in Response to Exercise.. Endocrinology Journal Club Works in Progress. Tucson, Arizona: Department of Medicine, Division of Endocrinology, University of Arizona.More infoZapata-Bustos R. Proteomic Analysis of the Vastus Lateralis from Lean and Obese Subjects: Evaluation of the Acetylome in Response to Exercise. Department of Medicine, Division of Endocrinology, University of Arizona. Endocrinology Journal Club Works in Progress, November 1, 2016
- Zapata Bustos, R. (2015, January). PGC-1 and muscle mitochondrial dysfunction in diabetes. Mayo/ASU Center for Metabolic and Vascular Biology Weekly Journal Club.. Scottsdale, Arizona: Mayo/ASU Center for Metabolic and Vascular Biology.More infoZapata-Bustos R. PGC-1 and muscle mitochondrial dysfunction in diabetes. Mayo/ASU Center for Metabolic and Vascular Biology Weekly Journal Club. January 28, 2015
Poster Presentations
- Mandarino, L. J., Grandjean, D. N., De Filippis, E. A., Coletta, D. K., Langlais, P. R., & Zapata Bustos, R. (2020, June/Summer). Lower Response of Connective Tissue Growth Factor (CTGF) to Exercise Characterizes Insulin Resistant Muscle. American Diabetes Association 80th scientific sessions. Chicago, IL: American Diabetes Association.More infoRocio Zapata-Bustos, Paul Langlais, Dawn Coletta, Elena A. De Filippis, Danielle Grandjean, Lawrence J. MandarinoLower Response of Connective Tissue Growth Factor (CTGF) to Exercise Characterizes Insulin Resistant Muscle