Developmental origins of adult diseases (fetal programming); Epigenetic regulation of stem cell differentiation; myogenesis and adipogenesis
Our research is focused on the epigenetic regulation of fetal development, focusing on skeletal muscle and adipose tissue. Specifically, we are interested in exploring mechanisms regulating the differentiation of mesenchymal stem cells into myocytes and adipocytes, and the impact of maternal physiological conditions on the development of fetal skeletal muscle and adipose tissue.
For human health, obesity, including maternal obesity, is increasing at an alarming rate. Skeletal muscle is the major tissue responsible for glucose and fatty acid utilization, and excessive adipose tissue is responsible for obesity. Both skeletal muscle and adipose tissue are primarily developed during the fetal stage. Abnormal muscle and adipose development of the fetuses or neonates due to maternal obesity pre-dispose offspring to adult diseases such as obesity and type II diabetes. But the underlying mechanisms remain poorly defined. Currently, we are exploring the impact of maternal nutrition on the expression of key transcription factors initiating early adipogenic and myogenic commitment of progenitor cells.
For animal agriculture, maternal nutrition especially under-nutrition impacts fetal muscle development and the subsequent animal performance and meat quality. Maternal nutrient deficiency permanently reduces offspring muscle mass but increases fatness. Low lean/fat ratio is associated with huge waste in animal production. On the other hand, intramuscular fat (marbling) is critically important for the palatability of meat. Because both adipocytes and muscle cells are developed from a common pool of progenitor cells, effective manipulation of progenitor cell differentiation can profoundly affect animal production efficiency and meat quality.
Our objective is to define mechanisms, especially environmental factors such as nutrition, which regulate the differentiation of mesenchymal progenitor cells into myocytes and adipocytes during fetal development. These studies have applications to both human medicine and animal agriculture.
We use in vitro cell culture, transgenic mice and livestock as experimental models. A wide range of laboratory techniques are used in our studies, including chemical analyses, enzyme activity assays, immunoblotting, ELISA, immunohistochemical staining, 2-dimensional gel electrophoresis and proteomic analyses, real-time PCR, DNA manipulation, RNA interference and epigenetic analyses.
(For complete publication list, visit Research Gate: https://www.researchgate.net/profile/Min_Du4)
Zou, T., et al. (2018). Raspberry promotes brown and beige adipocyte development in mice fed high-fat diet through activation of AMP-activated protein kinase (AMPK) a1. Journal of Nutritional Biochemistry, Feb 13;55:157-164. doi: 10.1016/j.jnutbio.2018.02.005.
Gao, J., et al. (2018). Bovine beta-lactalbumin hydrolysates (beta-LAH) ameliorate adipose insulin resistance and inflammation in high-fat-diet-fed C57BL/6J mice. Nutrients, 10, 242; doi:10.3390/nu10020242
Ma, Y. N., et al. (2018). Three dimensional spheroid culture of adipose stromal vascular cells for studying adipogenesis in beef cattle. Animal, Feb 22:1-7. doi:10.1017/S1751731118000150.
Sun, X., X. et al. (2018). Ex vivo gut culture for tracing gut epithelial development. Open Biology, In press.
Sun, X., et al. (2018). Purple potato extract promotes intestinal epithelial differentiation and barrier function by activating AMP-activated protein kinase. Molecular Nutrition and Food Research, Feb;62(4). doi: 10.1002/mnfr.201700536.
Son, J. S., et al. (2018). Exercise-induced myokines: a brief review of controversial issues of this decade. Expert Review of Endocrinology & Metabolism, 13: 51-58
Maricelli, J., et al. (2017). "Systemic Smad7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner." Hum Gene Ther. Nov 10. doi: 10.1089/hum.2017.158.
Song, J. J., et al. (2017). "Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates." J Dairy Sci 100(9): 6885-6894.
Sun, X., et al. (2017). "AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression." Cell Death Differ 24(5): 819-831.
Wang, B., et al. (2017). "Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRalpha+ adipose progenitors." Cell Discov 3: 17036.
Wang, B., et al. (2017). "Retinoic acid inhibits white adipogenesis by disrupting GADD45A-mediated Zfp423 DNA demethylation." J Mol Cell Biol 9(4): 338-349.
Wang, S., et al. (2017). "Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) alpha1 in mice fed high-fat diet." Mol Nutr Food Res 61(4).
Xue, Y., et al. (2017). "Escherichia coli O157:H7 suppresses host autophagy and promotes epithelial adhesion via Tir-mediated and cAMP-independent activation of protein kinase A." Cell Death Discov 3: 17055.
Xue, Y., et al. (2017). "Quercetin suppresses NLRP3 inflammasome activation in epithelial cells triggered by Escherichia coli O157:H7." Free Radic Biol Med 108: 760-769.
Bibi, S., et al. (2017). "Maternal high-fat diet consumption enhances offspring susceptibility to DSS-induced colitis in mice." Obesity (Silver Spring) 25(5): 901-908.
Fu, X., et al. (2017). "Reduced satellite cell density and myogenesis in Wagyu compared with Angus cattle as a possible explanation of its high marbling." Animal: 1-8.
Griner, J. D., et al. (2017). "Lysyl oxidase propeptide promotes adipogenesis through inhibition of FGF-2 signaling." Adipocyte 6(1): 12-19.
Guan, L., et al. (2017). "bta-miR-23a involves in adipogenesis of progenitor cells derived from fetal bovine skeletal muscle." Sci Rep 7: 43716.
Kang, Y., et al. (2017). "Preventive effects of Goji berry on dextran-sulfate-sodium-induced colitis in mice." J Nutr Biochem 40: 70-76.
Li, T., et al. (2017). "Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells." Nutrients 9(1).
Song, J. J., et al. (2017). "Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling." Mol Nutr Food Res 61(2).
Wang, B., et al. (2017). "Maternal Retinoids Increase PDGFRalpha+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development." EBioMedicine 18: 288-299.
Wang, B., et al. (2017). "Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling." FASEB J 31(10): 4612-4622.
Chen, Y., et al. (2017). Constructing a comprehensive gene co-expression based interactome in Bos Taurus. PeerJ, 5: e4107.
Wang, B., F. et al. (2017). Alcohol intake aggravates adipose browning and muscle atrophy in cancer associated cachexia. Oncotarget, 8: 100411-100420.
Bibi, S., et al. (2017). Dietary red raspberries attenuate dextran sulfate sodium-induced acute colitis. Journal of Nutritional Biochemistry, 51: 40-46.
Gao, P. F., et al. (2017). LncRNAs profiling of skeletal muscles in Large White pigs and Mashen pigs during development. Journal of Animal Science, 95: 4239-4250.
Li, T., et al. (2017). Upregulation of heme oxygenase-1 mediates the anti-inflammatory activity of casein glycomacropeptide (GMP) hydrolysates in LPS-stimulated macrophages. Food & Function, 8: 2475-2484.
Zhao, J., et al. (2017). AMPKa1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development. Biochemical and Biophysical Research Communications, 491: 508-514.
Du, M., et al. (2017). Optimizing livestock production efficiency through maternal nutritional management and fetal developmental programming. Animal Frontiers, 7: 5-11.
Sun, X. et al. (2017). AMPK regulate intestinal differentiation via histone modification of CDX2. Cell Death and Differentiation, 24: 819-831.
Yang, G., et al. (2017). Regulation of the intestinal tight junction by natural polyphenols: a mechanistic perspective. Critical Reviews in Food Science and Nutrition, 595: 1547-1562.
Wang B., et al. (2017). Maternal retinoids increase PDGFRa progenitor population and beige adipogenesis in progeny by stimulating vascular development. EBioMedicine, 18: 288-299.
Zou, T., et al. (2017). Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. Journal of Physiology, 595: 1547-1562.
Xue, Y., et al. (2017). Dandelion extract suppresses reactive oxidative species and inflammasome in intestinal epithelial cells. Journal of Functional Food, 29: 10-18.
Campos, C. F., et al. (2016). "Review: Animal model and the current understanding of molecule dynamics of adipogenesis." Animal 10(6): 927-932.
Fu, X., et al. (2016). "Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK." Diabetes 65(1): 188-200.
Liang, X., et al. (2016). "Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice." J Physiol 594(15): 4453-4466.
Miao, Z. G., et al. (2016). "Invited review: mesenchymal progenitor cells in intramuscular connective tissue development." Animal 10(1): 75-81.
Wang, B., et al. (2016). "Nutrigenomic regulation of adipose tissue development - role of retinoic acid: A review." Meat Sci 120: 100-106.
Wei, S., et al. (2016). "Long noncoding RNAs in regulating adipogenesis: new RNAs shed lights on obesity." Cell Mol Life Sci 73(10): 2079-2087.
Li, N., et al. (2016). "Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis." Endocrinology 157(1): 282-291.
Liang, X., et al. (2016). "Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice." Sci Rep 6: 34345.
Yang, Q., et al. (2016). "AMPK/alpha-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis." Cell Metab 24(4): 542-554.
Zhang, H., et al. (2016). "Butyrate suppresses murine mast cell proliferation and cytokine production through inhibiting histone deacetylase." J Nutr Biochem 27: 299-306.
Song, J., et al. (2016). Sea cucumber peptides exert anti-inflammatory activity through suppressing NF-kB and MAPK and inducing HO-1 in RAW264.7 macrophages. Food & Function, 7: 2773-2779.
Yang, Q., et al. (2016). AMPK/α-ketoglutarate axis dynamically mediates DNA demethylation in the Prdm16 promoter and brown adipogenesis. Cell Metabolism, 24: 542-554. (This paper was featured in Editors’ Choice, Science Signaling: Nancy R. G., Improving the health of newborns of obese mothers. Sci. Signal. 2016, 451: ec246)
Zhu, H. et al. (2016). Bactericidal effects of Cinnamomum cassia oil against bovine mastitis bacterial pathogens. Food Control, 66: 291-299.
Bibi, S., et al. (2016). Grape seed extract improves small intestinal morphology through suppressing inflammation and regulating alkaline phosphatase in IL10-deficient mice. Journal of Functional Foods, 20: 245-252.
Fu, X., et al. (2016). Obesity impairs skeletal muscle regeneration via inhibition of AMP-activated protein kinase. Diabetes, 65: 188-200.
Martins, T. S., et al. (2015). "Molecular Factors Underlying the Deposition of Intramuscular Fat and Collagen in Skeletal Muscle of Nellore and Angus Cattle." PLoS One 10(10): e0139943.
Wang, S., et al. (2015). "Prevention of obesity by dietary resveratrol: how strong is the evidence?" Expert Rev Endocrinol Metab 10(6): 561-564.
Chen, D., et al. (2015). "Sequencing and Characterization of Divergent Marbling Levels in the Beef Cattle (Longissimus dorsi Muscle) Transcriptome." Asian-Australas J Anim Sci 28(2): 158-165.
Dodson, M. V., et al. (2015). "INVITED REVIEW: Evolution of meat animal growth research during the past 50 years: Adipose and muscle stem cells." J Anim Sci 93(2): 457-481.
Du, M., et al. (2015). "Fetal programming in meat production." Meat Sci 109: 40-47.
Wang, S., et al. (2015). "Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) alpha1." Int J Obes (Lond) 39(6): 967-976.
Wei, S., et al. (2015). "Enhanced mitogenesis in stromal vascular cells derived from subcutaneous adipose tissue of Wagyu compared with those of Angus cattle." J Anim Sci 93(3): 1015-1024.
Fu, X., et al. (2015). "AMP-activated protein kinase stimulates Warburg-like glycolysis and activation of satellite cells during muscle regeneration." J Biol Chem 290(44): 26445-26456.
Yang, G., et al. (2015). "Favourable effects of grape seed extract on intestinal epithelial differentiation and barrier function in IL10-deficient mice." Br J Nutr 114(1): 15-23.
Yang, G., et al. (2015). Favorable effects of GSE on intestinal epithelial differentiation and barrier function in IL10-deficient mice. British Journal of Nutrition, 114: 15-23.
Duarte, M. S., et al. (2014). "Maternal overnutrition enhances mRNA expression of adipogenic markers and collagen deposition in skeletal muscle of beef cattle fetuses." J Anim Sci 92(9): 3846-3854.
Meyer, A. M., et al. (2014). "Small intestinal growth measures are correlated with feed efficiency in market weight cattle, despite minimal effects of maternal nutrition during early to midgestation." J Anim Sci 92(9): 3855-3867.
Wang, B., et al. (2014). "Grape seed extract prevents skeletal muscle wasting in interleukin 10 knockout mice." BMC Complement Altern Med 14: 162.
Xue, Y., et al. (2014). "Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice." J Nutr Biochem 25(7): 758-764.
Xue, Y., et al. (2014). "Host inflammatory response inhibits Escherichia coli O157:H7 adhesion to gut epithelium through augmentation of mucin expression." Infect Immun 82(5): 1921-1930.
Du, M. (2014). "MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--implants, muscle development, and meat quality." J Anim Sci 92(1): 1-2.
Hur, S. J., et al. (2014). "Effects of dietary cholesterol and its oxidation products on pathological lesions and cholesterol and lipid oxidation in the rabbit liver." Biomed Res Int 2014: 598612.
Wang, H., et al. (2014). "Maternal obesity exacerbates insulitis and type 1 diabetes in non-obese diabetic mice." Reproduction 148(1): 73-79.
Zhang, H., et al. (2014). "Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice." World J Gastroenterol 20(27): 9106-9115.
Zhu, M. J., et al. (2014). "CELL BIOLOGY SYMPOSIUM: Impacts of maternal obesity on placental and gut inflammation and health." J Anim Sci 92(5): 1840-1849.
Hausman, G. J., et al. (2014). Intermuscular and intramuscular adipose tissues: bad vs. good adipose tissues. Adipocytes, 3: 242-255.
Dodson, M.V., et al. (2014). Adipose depots differ in cellularity, adipokines produced, gene expression and cell systems. Adipocyte, 3: 323-328.
Xue, Y., et al. (2014). Maternal obesity induce gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice. Journal of Nutritional Biochemistry, 25: 758-764.