NEUROENDOCRINOLOGY

Obesity is globally epidemic, and it is associated with the high risk of several serious diseases, including type 2 diabetes. Obesity occurs when there is an imbalance between energy intake and energy expenditure. Energy balance is primarily controlled by a brain region called hypothalamus, where highest concentration of neuropeptide Y (NPY) is found, and the activation of NPY at hypothalamic arcuate nucleus potently stimulates food intake and reduces energy expenditure. There are 3 ligands in NPY family, NPY, PYY and PP, and they exert their actions via at least 5 GPCR receptors: Y1, Y2, Y4, Y5 and y6.

Our primary research focus is the neuroendocrine regulation of food intake, adipose tissue thermogenesis & metabolism, insulin secretion and glucose homeostasis, with a special emphasis on evaluating the critical actions of centrally- and peripherally-produced NPY, PYY and PP and their receptors in these processes. By using novel germline and conditional transgenic and knockout mouse models and cutting edge molecular techniques, we have been investigating the phenotypic characterisations of energy balance in mouse models and dissecting the associated molecular mechanisms and neuronal pathways. More recently, we have been active in elucidating the role of PYY and Y1 receptors (Y1R) in the control of insulin secretion in pancreatic islets 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.

In 2013, we discovered 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. In 2017, our research identified Y1R in beta cells act as a brake to inhibit insulin release, and pharmacological blockade enhances insulin secretion, which can be harnessed for improving islet transplant efficiency in diabetic mice and human. Thus, our novel research findings have contributed to a better understanding of fundamental processes in obesity and diabetes with potential to develop therapeutical targets for the treatment of obesity and diabetes.

We are currently recruiting PhD students and Honours students to conduct projects that are funded by the NHMRC. Undergraduate Research Opportunity Program (UROP) students are also welcome.

Selected Publications

Lau J, Farzi A, Qi Y, Heilbronn R, Mietzsch M, Shi YC*, Herzog H*. CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis. Molecular Metabolism. Jan 2018  (*As co-corresponding author)

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. Sep 2017 (# Co-first author).

Lau J, Farzi A, Enriquez RF, Shi YC*, Herzog H*. GPR88 is a critical regulator of feeding and body composition in mice. Scientific Reports. July 2017 (*As co-corresponding 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. May 2017 (*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.  Mar 2017

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. Dec 2016 

Lau J, Shi YC*, Herzog H*. Temperature dependence of the control of energy homeostasis requires CART signaling. Neuropeptides. Apr 2016 (*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. Jan 2016

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. Sep 2015 (*Corresponding author)

Loh K, Herzog H*, Shi YC*. Regulation of energy homeostasis by the NPY system. Trends Endocrinol Metab. Mar 2015 (*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. Oct 2014

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. June 2014

Yulyaningsih E; Loh K; Lin S; Lau J; Zhang L; Shi YC; 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, Jan 2014

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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