Dr. Kai Sun, MD, PhD

Dr. Kai Sun, MD, PhD

Assistant Professor, Center for Metabolic & Degenerative Diseases

Email Address: Kai.Sun@uth.tmc.edu
Phone Number: 713-500-3190
Room Number: SRB 437A

Narrative

Dr. Sun received his medical degree in preventive medicine from West China University of Medical Sciences, MPH from Beijing Medical University, and  PhD from University of California, Riverside. His Postdoctoral training in Dr. Philipp Scherer’s laboratory at UT Southwestern Medical Center entailed remodeling of adipose tissue during obesity development, including studies of hypoxia, angiogenesis, and fibrosis in obese fat pads. Dr. Sun’s research interests lie in factors derived from adipose tissue that influence function and dysfunction of adipose tissue. 

Obese fat pads are frequently undervascularized and hypoxic which further cause increased fibrosis, inflammation, and ultimately insulin resistance. Dr. Sun has demonstrated that the effects of modulation of angiogenic activity in fat tissue could be dichotomous and metabolic context dependent. The pace of the fat pad expansion during metabolic insults determines the final outcome: in healthily expanded adipose tissue, angiogenesis is beneficial by improving vascularization and inducing a “browning” of white adipocytes. In contrast, in pathologically expanded adipose tissue, antiangiogenic action leads to improvements in metabolism by ablating dysfunctional adipocytes.

Dr. Sun further explores the fine-tuned regulation at other levels during the pathological expansion of adipose tissue. Indeed, He found fibrosis is the hallmark in the metabolically dysfunctional adipose tissue. Interestingly, his recent research suggested that the regulation of ECM flexibility by MMPs is also metabolic context dependent: On the one hand, at early stages of obesity, MT1-MMP cleaves collagenous proteins and stimulates angiogenesis in combination with VEGF and leptin, thus relieving the pathological conditions caused by hypoxia; On the other hand, in the context of  pre-existing unhealthy adipose tissue, it digests COL6α3 and produces endotrophin which accelerates fibrosis and inflammation, ultimately leading a highly unfavorable microenvironment to sustain metabolic flexibility.

Research Projects

  • Hypoxia stimulated fibrosis and local inflammation in adipose tissue.
  • Mechanisms by which angiogenic factors stimulate white adipocytes “browning” during early stage of obesity development (healthy expansion).
  • The effects of antiangiogenic action by blocking VEGF-A and/or its receptors in the context of preexisting adipose tissue (unhealthy expansion).
  • Reversibility of adipose tissue fibrosis by MT1-MMP (MMP14) and novel anti-fibrotic therapies for the treatment and prevention of obesity and diabetes.
  • The mechanisms by which MT1-MMT exerts profound pathophysiological effects in preexisted unhealthy fat tissue

Recent Publications

  • Zhao Y, Gu X, Zhang NY, Kolonin MG, An ZQ and Sun K. “Divergent functions of endotrophin on different cell populations in adipose tissue”. AJP-Endo&Metab. (In press, 2016).
  • Sun K, Park J, Gupta O, Holland WL, Auerbach PL, Zhang N, Marangoni RG, Nicoloro SM, Czech MP, Varga J, Ploug T, An ZQ and Scherer PE. “Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction”.Nature Commun. 5:3485. (2014).
  • Sun KKusminski CM, Luby-Phelps K , Spurgin, SB , An YA , Wang QA, Holland, WL and Scherer, PE.“Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure”  Mol. Metab. 3(4): 471-28 (2014).
  • Kim M, Neinast MD, Frank AP, Sun K, Park J, Zehr JA, Vishvanath L, Morselli E, Amelotte M, Palmer BF, Gupta RK, Scherer PE, Clegg DJ. “ERalpha upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue”. Mol. Metab. 3(6): 642-51. (2014)
  • Liu C, Bookout AL, Lee S, Lee C, Sun K, Jia L, Udit S, Deng Y, Scherer PE, Mangelsdorf DJ, Gautron L, Elmquist JK . “PPARγ in vagal sensory neurons regulates high-fat diet induced thermogenesis”. Cell Metab.19 (4):722–30(2014).
  • Jia L, Vianna C, Fukuda M, Berglund E, Liu C, Sun K, Tao C, Liu T, Harper M, Lee CE, Scherer PE, Elmquist JK. “Hepatocyte toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance. Nature Commun. 5:3878. (2014).
  • Bueno AC, Sun K, Martins C, Elias Junior J, Miranda W, Tao C, Cristina Foss-Freitas M, Barbieri MA, Bettiol H, de Castro M, Scherer PE, Antonini SR.“A Novel ADIPOQ Mutation (p.M40K) impairs assembly of high-molecular-weight adiponectin and is associated with early-onset obesity and metabolic syndrome”. J Clin Endocrinol Metab. 99(4): E683-93. (2014).
  • Sun KTordjman J, Clément K, and Scherer PE “Fibrosis and adipose tissue dysfunction”. Cell Metab. 18(4):470-7. (2013).
  • Sun K, Halberg N, Khan M, Magalang UJ, Scherer PE. “Selective inhibition of hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction”. Mol Cell Biol. 33(5):904-17. (2013)
  • He C, Wei Y*, Sun K*Li B*, Zou Z, Liu Y, Kinch LN, Khan S, Xavier RJ, Grishin NV, Xiao G, Eskelinen EL, Scherer PE, Whistler JL, and Levine B. “Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism” (* contributed equally). Cell. 154(5):1085-99. (2013)
  • Davis KE, Neinast M, Sun K, Skiles W, Bills J, Zehr J, Zeve D, Hahner L, Cox D, Gent L, Xu Y, Wang ZV, Khan S, Clegg DJ “The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis”.  Mol. Metab2(3):227-42. (2013).
  • He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby R, Scherer PE, and Levine B. “Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis”. 481(7382):511-5. (2012).
  • Sun K, Wernstedt Asterholm I, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, Brekken RA, Scherer PE. “Dichotomous effects of VEGF-A on adipose tissue dysfunction”. Proc Natl Acad Sci U S A. 109(15):5874-9. (2012).
  • Sun K, Scherer PE. “The PPARγ-FGF1 axis: an unexpected mediator of adipose tissue homeostasis”. Cell Res. 22(10):1416-8. (2012).
  • Kusminski CM, Holland WL, Sun K, Park J, Spurgin SB, Lin Y, Askew GR, Simcox JA, McClain DA, Li C, Scherer PE. “MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity”. Nat Med. 18(10):1539-49. (2012).
  • Sun KKusminski CM, Scherer PE. “Adipose tissue remodeling and obesity”. J Clin Invest. 121 (6): 2094-101(2011).
  • Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE. “Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin”. Nat Med. 17 (1):55-63. (2010).
  • Wang ZV, Deng Y, Wang QA, Sun K, and Scherer PE. “Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression”. Endocrinology. 151(6):2933- 9. (2010).