Dr. Sun is an expert on “hunger hormone” ghrelin. She generated the first ghrelin knockout mice, and discovered ghrelin’s novel roles in diabetes, thermogenesis and macrophage polarization. Her laboratory uses state-of-the-art tools to study ghrelin in energy sensing, intake, and expenditure. Her work suggests that ghrelin might be a promising drug target for obesity, diabetes, inflammation, and aging.

Glucose-homeostasis, energy-homeostasis, lipid metabolism, neuroendocrine regulation, pathogenesis and pathophysiology of obesity, diabetes, inflammation, and aging.

The incidence of obesity and diabetes has reached epidemic proportions worldwide. The primary cause of diabetes is obesity, which often leads to insulin resistance. Insulin resistance eventually causes pancreatic beta cell failure, resulting in diabetes.

Ghrelin is the only known orexigenic hormone. It increases growth hormone (GH) release, stimulates appetite and promotes obesity. To study the physiological functions of ghrelin signaling, Dr. Sun generated knockout mice for ghrelin and the ghrelin receptor (aka, growth hormone secretagogue receptor, GHS-R), and discovered that ablation of ghrelin improves pancreatic beta cell function, reducing hyperglycemia of diabetic mice.

Obesity is centered in adipose tissues, which consist of white adipose tissue (WAT) and brown adipose tissue (BAT). While WAT stores energy, BAT burns energy to generate heat (thermogenesis). The thermogenic capacity of BAT is decreased in obese subjects and the elderly. Dr. Sun’s team reported that ablation of GHS-R increases BAT thermogenesis during aging, leading to a lean and insulin-sensitive phenotype. In addition, they found that deletion of GHS-R shifts macrophages from pro-inflammatory to anti-inflammatory, reducing adipose and hepatic inflammation.  Thus, GHS-R ablation switches adipose tissues from obesogenic to thermogenic, and shifts macrophages from pro-inflammatory to anti-inflammatory. The work of Dr. Sun’s lab collectively suggests that targeting the ghrelin-signaling may represent a novel strategy for treatment of obesity and diabetes; GHS-R antagonists may promote weight loss by burning fat, and reducing inflammation by modulating macrophage phenotypic switch.

Ongoing projects are to elucidate the roles and pertinent mechanisms of ghrelin-signaling in obesity, diabetes, inflammation and aging. Specifically to investigate the roles of ghrelin signaling in: 1) glucose homoeostasis and insulin resistance; 2) energy balance and neuroendocrine regulation; 3) macrophage-mediated inflammation and immunometabolism. Physiological and pharmacological approaches are carried out in global and tissue-specific knockout and knockin mice, as well as in primary cells and tissue culture systems.

The ultimate goal of Dr. Sun’s team is to understand the pathogenesis and pathophysiology of obesity and diabetes, inflammation and aging, and to develop novel interventions for combating obesity and diabetes, thus improving quality of life.

https://scholar.google.com/citations?user=AvEn46EAAAAJ&hl=en

1. Lee JH, Lin L, Xu P, Saito K, Wei Q, Meadows AG, Bongmba OY, Pradhan G, Zheng H, Xu Y, Sun Y. (2016).  Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity. Diabetes 65: 2169-2178.
2. Lin L, Lee JH, Buras ED, Smith CW, Wu H, Sheikh-Hamad D, Sun Y (2016). Ghrelin receptor regulates adipose tissue inflammation in aging. Aging (in press).
3. Yuxiang Sun (2015). Ghrelin controls obesity by burning fat. Oncotarget 6:6470-6471.
4. Lin L^#, Lee JH^#, Bongmba OY, Ma X, Zhu X, Sheikh-Hamad D, Sun Y (2014). The suppression of ghrelin signaling mitigates age‐associated thermogenic impairment. Aging 6:1019-1032.
5. Porporato PE, Filigheddu N, Gnocchi VF, Reano S, Ardisson GB, Fornaro M, Ronchi G, Fagoonee S, Chianale F, Baldanzi G, Surico N, Perroteau I, Smith RG, Sun Y, Geuna S, Graziani A (2013). Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. Journal of Clinical Investigation 123:611-22.
6. Ma X, Lin L, Yue J, Pradhan G, Qin G, Minze LJ, Wu H, Sheikh-Hamad D, Smith CW, Sun Y (2013). Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance. Nutrition & Diabetes 3:e99.
7. Pradhan G, Samson SL, Sun Y (2013). Ghrelin: much more than a hunger hormone. Curr Opin Clin Nutr Metab Care. 16:619-624. PMID:24100676.
8. Lin L, Saha PK, Ma X, Henshaw IO, Shao L, Chang BH, Buras ED, Tong Q, Chan L, McGuinness OP, Sun Y * (2011) Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues. Aging Cell 10:996-1010.
9. Sun Y, Asnicar M and Smith RG. (2007). Central and peripheral roles of ghrelin on glucose homeostasis. Neuro-endocrinology 86:215-228.
10. Sun Y, Asnicar M, Saha PK, Chan L and Smith RG. (2006). Ablation of Ghrelin Gene Improves the Diabetic but not Obese Phenotype of ob/ob Mice. Cell Metabolism 3:379-386.
11. Sun Y, Wang P, Zheng H and Smith RG. (2004). Growth Hormone Secretagogue Receptor (GHS-R) mediates ghrelin’s effects on GH release and appetite. Proc Natl Acad Sci USA 101:4679-4684.