Obesity is associated with several health conditions, the most devastating of which is type 2 diabetes. Obesity occurs when energy intake exceeds energy expenditure. Current weight loss therapies targeting the reduction of food intake have proven to be relatively ineffective, and the ability to reduce the risk of obesity-related complications is limited. Energy balance is controlled by a brain region called hypothalamus, whose neuronal inputs and outputs are also critical in the regulation of glucose homeostasis.
Our primary research focus is the neuroendocrine regulation of food intake, energy homeostasis and glucose metabolism, with a special emphasis on evaluating the critical actions of centrally- and peripherally-produced NPY, PYY and PP in these processes, including the molecular mechanisms and neuronal pathways underlying these actions by using germline and conditional transgenic and knockout mouse models available and molecular techniques. More recently, we have been particularly active in elucidating the role of neuropeptide Y family including PYY and their receptors in the control of insulin synthesis and secretion as well as glucose metabolism through direct neural signalling and modulation of local endocrine function. In addition we have been interested in examining the important interplay between adipose tissue and bone.
Our recent work has identified critical brain circuits that could explain the clinical phenomenon that the harder some obese people diet, the harder it is for them to lose weight. Our novel research findings have contributed to a better understanding of these fundamental processes with potential to develop therapeutical targets for the treatment of obesity and its most ominous complication, diabetes.
Loh K#, Shi YC#, Walters S#, Bensellam M ,Lee K, Dezaki K, Nakata M, Ip CK, Chan J, Gurzov EN, Thomas HE, Waibei M, Cantley J, Kay TM, Yada T, Laybutt DR, Grey S and Herzog H. Inhibition of Y1 receptor signaling improves islet transplant outcome. Nature Communications. July 2017 (Accepted). (# Co-first author).
Shi YC*, Ip CK, Reed F, Sarruf DA, Wulff BS, Herzog H. Y5 receptor signalling counteracts the anorectic effects of PYY3-36 in diet induced obese mice. J Neuroendocrinol. 2017 May 9.(*Corresponding author)
Sun WW, Li LY, Huang XF, Shi YC, Yang HQ, Song ZY, Lin S. The central mechanism of risperidone-induced hyperprolactinemia. Progress in Neuropsychopharmacol Biol Psychiatry. 2017 Mar 20;76:134-139.
Worton LE, Shi YC, Smith E, Barry S, Gonda T, Whitehead J, Gardiner EM. Ectodermal-neural cortex 1 isoforms have contrasting effects on MC3T3-E1 osteoblast mineralization and gene expression. J Cellular Biochemistry 2016 Dec.
Lau J, Shi YC*, Herzog H*. Temperature dependence of the control of energy homeostasis requires CART signaling. Neuropeptides. 2016; Apr 5. pii: S0143-4179(16)30031-2.(*Corresponding author)
Seimon RV, Shi YC, Slack K, Lee K, Fernando HA, Nguyen AD, Zhang L, Lin S, Enriquez RF, Lau J, Herzog H, Sainsbury A. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice. PLoS One. 2016; Jan 19;11(1):e0145157.
Shi YC*, Loh K, Bensellam M, Lee K, Zhai L, Lau J, Cantley J, Luzuriaga J, Laybutt DR, Herzog H. Pancreatic PYY Is Critical in the Control of Insulin Secretion and Glucose Homeostasis in Female Mice. Endocrinology. 2015; Sep;156(9):3122-36. (*Corresponding author)
Loh K, Herzog H*, Shi YC*. Regulation of energy homeostasis by the NPY system. Trends Endocrinol Metab. 2015; Mar;26(3):125-35.(*Corresponding author)
Baldock PA, Lin S, Zhang L, Karl T, Shi Y, Driessler F, Zengin A, Hörmer B, Lee NJ, Wong IPL, Lin EJD, Enriquez RF, Stehrer B, During MJ, Yulyaningsih E, Zolotukhin S, Ruohonen ST, Savontaus E, Sainsbury A, Herzog H. 'Neuropeptide Y attenuates stress-induced bone loss through suppression of noradrenaline circuits', Journal of Bone and Mineral Research, 2014; vol. 29, no. 10, pp. 2238 - 2249.
Nguyen AD, Slack K, Schwarzer C, Lee NJ, Boey D, Macia L, Yulyaningsih E, Enriquez RF, Zhang L, Lin S, Shi YC, Baldock PA, Herzog H, Sainsbury A. Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice. Neuropeptides. 2014; Jun;48(3):143-51.
Yulyaningsih E; Loh K; Lin S; Lau J; Zhang L; Shi Y; Berning BA; Enriquez R; Driessler F; Macia L; Khor EC; Qi Y; Baldock P; Sainsbury A; Herzog H, 'Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice', Cell Metabolism, 2014; vol. 19, no. 1, pp. 58 - 72.
Shi YC, Lin Z, Lau J, Zhang H, Yagi M, Kanzler I, Sainsbury A, Herzog H, Lin S. PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice. Obesity. 2013; Dec;21(12):E669-78.
Shi YC, Lau J, Lin Z, Zhang H, Zhai L, Sperk G, Heilbronn R, Mietzsch M, Weger S, Huang XF, Enriquez RF, Castillo, L., Baldock PA, Zhang L, Sainsbury A, Herzog H & Lin S. Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN. Cell Metabolism. 2013; 17(2):236-48
Macia L, Yulyaningsih E, Bijker M, Pangon L, Nguyen AD, Lin S, Shi YC, Zhang L, Mackay F, Sainsbury A, Herzog H. Neuropeptide Y1 receptor in immune cells regulates inflammation and insulin resistance associated with diet-induced obesity. Diabetes. 2012; 61(12):3228-38
Shi YC, Hämmerle C, Lee I-C, Turner N, Nguyen AD, Riepler SJ, Sainsbury A, Herzog H, Zhang L. Adult-onset PYY overexpression in mice reduces food intake and increased lipogenic capacity. Neuropeptides. 2012; 46(4):173-82
Shi YC & Baldock P. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue. Bone. 2012; 50(2):430-6
Shi YC, Lin S, Castillo L, Aljanova A, Enriquez RF, Nguyen AD, Baldock PA, Zhang L, Bijker MS, Macia L, Yulyaningsih E, Zhang H, Lau J, Sainsbury A, Herzog H. Peripheral-specific Y2 receptor knockdown protects mice from high-fat diet-induced obesity. Obesity. 2011; 19(11): 2137-48
Shi YC, Lin S, Wong IP, Baldock PA, Aljanova A, Enriquez RF, Castillo L, Mitchell NF, Ye JM, Zhang L, Macia L, Yulyaningsih E, Nguyen AD, Riepler SJ, Herzog H, Sainsbury A. NPY neuron-specific Y2 receptors regulate adipose tissue and trabecular bone but not cortical bone homeostasis in mice. PLoS One. 2010; 5(6): e11361
Lin S, Shi YC, Yulyaningsih E, Aljanova A, Zhang L, Macia L, Nguyen AD, Lin EJ, During MJ, Herzog H, Sainsbury A. Critical role of arcuate Y4 receptors and the melanocortin system in pancreatic polypeptide-induced reduction in food intake in mice. PLoS One. 2009; 4(12):e8488.
Shi YC, Worton L, Esteban L, Baldock P, Fong C, Eisman JA, Gardiner EM. Effects of continuous activation of vitamin D and Wnt response pathways on osteoblastic proliferation and differentiation. Bone. 2007; 41(1): 87-96.
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