The hypothalamus is a key element of the neural circuits that regulate energy and glucose homeostasis. Specific neuronal populations within the hypothalamus are sensitive to a variety of homeostatic indicators, such as circulating nutrients and hormones (e.g., insulin, ghrelin, leptin) that signal circulating glucose, gut nutrient, and body fat content. My research program focuses on studying the neurobiology of energy metabolism in general and hypothalamic neural mechanisms associated with metabolic dysregulation and obesity in particular. The major goal of my lab is to construct the neural circuits that control energy metabolism using cutting-edge technology such as conditional viral tracing, wired and wireless optogenetics, pharmacogenetics, in vivo calcium imaging, in vivo fiber photometry, CRISPR/Cas-9 gene-knockdown, and electrophysiology. 

The liver plays a major role in controlling energy metabolism, including macronutrient metabolism, lipid homeostasis, and energy storage. The role of the autonomic nervous system – and the parasympathetic nervous system in particular – on hepatic metabolism has been the focus of substantial debate and controversy. Despite much interest and several contradictory findings in the literature ranging from no role for vagal cholinergic innervation to glucose and lipid metabolism to an important role in their regulation in rodents and humans, the anatomy and function of the parasympathetic cholinergic innervation of the liver still remain poorly characterized. My lab seeks to determine the role of vagal cholinergic innervation of the liver in hepatic energy metabolism.

The liver function is also regulated by vagal sensory neurons located in the nodose ganglion. My goals are to determine: (1) whether a liver-brain neural circuit is essential for whole body energy metabolism and (2) whether this neural circuit plays a vital role in brain functions.  

Publications:

https://www.ncbi.nlm.nih.gov/myncbi/young-hwan.jo.2/bibliography/public/

Recent Publications (2012- present)

A. ORGAN-BRAIN CROSSTALK

1. Jo, YH, Differential transcriptional profiles of vagal sensory neurons in female and male mice. Front. Neurosci. 18:1393196 (2024)

B. HYPOTHALAMIC POMC NEURONS AND ENERGY METABOLISM

1. Choi YN, Min HY, Hwang JY, and Jo YH, Magel2 knockdown in hypothalamic POMC neurons innervating the medial amygdala reduces susceptibility to diet-induced obesity. Life Science Alliance (2022) PMCID: PMC9418835

2. Kwon EJ, Joung HY, Liu SM, Chua SC Jr, Schwartz GJ, and Jo YH, Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production. Nature Communications (2020); 11(1):6295. doi: 10.1038/s41467-020-20160-w

3. Kwon EJ and Jo YH,  Activation of the ARCPOMC->MeA projection reduces food intake. Frontiers in Neural circuits (2020)  https://doi.org/10.3389/fncir.2020.595783

4. Jeong JH, Lee DK, Liu S-M, Chua SC Jr., Schwartz GJ, and Jo YH, Activation of Temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake. PLOS Biology (2018), 16 (4):e2004399 (Research highlight in Nature, Top 10% cited article in PLOS biology in 2018-2019, Featured article in PLOS Biology)

5. Lee D.K., Jeong J.H., Chun S.-K., Chua S.C. Jr. and Jo Y.H  Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons. Nature Commun. (2015) 26;6:6618. doi: 10.1038/ncomms7618 

6. Lee DK, Jeong JH, Oh SH and Jo YH Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current. PLOS One (2015) Mar 17;10(3):e0119457

C. CENTRAL CHOLINERGIC REGULATION OF ENERGY METABOLISM

1. Jae Hoon Jeong, Dong Kun Lee, and Young-Hwan Jo, Cholinergic neurons in the dorsomedial hypothalamus regulates food intake. Molecular metabolism (2017), Jan 12;6(3):306-312 

2. Jeong J.H., Woo Y.J., Chua S.C., and Jo Y.H. Single-cell gene expression analysis of cholinergic neurons in the arcuate nucleus of the hypothalamus. PLOS One (2016) Sep 9;11(9):e0162839. doi: 10.1371/journal.pone.0162839

3. Jeong J.H., Lee DK, Blouet C, Ruiz H.H., Buettner C, Chua S.C., Schwartz G.J., and Jo Y.H. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism. Molecular metabolism (2015) 11;4(6):483-92  

4. Groessl F, Jeong JH, Talmage DA, Role LW and Jo YH, Overnight fasting regulates inhibitory tone to cholinergic neurons of the dorsomedial nucleus of the hypothalamus. PLOS One (2013) Vol. 8 (4), e60828 

D. REGULATION OF BROWN ADIPOSE TISSUE THERMOGENESIS

1. Min HY, Hwang JY, Choi YN, and Jo YH, Overexpressing the hydroxycarboxylic acid receptor 1 in mouse brown adipose tissue restores glucose tolerance and insulin sensitivity in diet-induced obese mice. AJP-Endocrinology and Metabolism (2022) PMCID: PMC9423771

2. Kwon EJ, Yoo TS, Joung HY, and Jo YH, Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet. PLOS One (2020) 15(1):e0228320

3. Jeong JH, Chang JS, and Jo YH, Intracellular glycolysis in brown adipose tissue is essential for optogenetically induced nonshivering thermogenesis in mice. Scientific Reports (2018) Apr 27;8(1):6672

E. REGULATION OF HYPOTHALAMIC NEURONS

1. Liu S, Marcelin G, Blouet C, Jeong JH, Jo YH, Schwartz GJ, Chua S Jr. A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus. Molecular metabolism (2017) Dec S2212-8778(17)30843-8

2. Marcelin G, Jo YH, Li X, Schwartz GJ, Zhang Y, Dun NJ, Lyu RM, Blouet C, Chang JK, Chua SC, Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Molecular Metabolism (2013) 23; 3(1):19-28 

3.  Byun K, Gil SY, Youn BS, Huang H,  Namkoong C, Jang PG, Lee JY, Jo YH, Kang GM, Kim HK, Shin MS,  Pietrzik  CU,  Lee B, Kim YB,  Kim MS, Clusterin  (ApoJ)  and  LRP2  are  critical components of the central leptin signaling pathway. Nature Comm. (2013)  4:1862 

4. Lu, Z , Marcelin G, Bauzon M, Wang H, Fu H, Dun SL, Zhao H, Li X, Jo YH, Wardlaw S, Dun N, Chua, S Jr.,and Zhu L., pRb is an obesity suppressor in hypothalamus and high]fat diet inhibits pRb in this location. EMBO (2013) 32(6):844-57 

5. Blouet, C., Lui, SM, Jo, YH, Li, X. and Schwartz, G., TXNIP in Agrp Neurons Regulates Adiposity, Energy Expenditure, and Central Leptin Sensitivity. J. Neurosci. (2012) Jul 18;32(29):9870-9877 

6. Israel, DD, Sheffer, Babila, S, de Luca, C, Jo, YH, Liu, SM, Xia, Q, Spergel, D, Dun, SK, Dun, NJ and Chua, SC, Effects of leptin and melanocortin signaling on pubertal development and reproduction. Endocrinology (2012) May; 153(5):2408-19  

7. Jo, YH, Endogenous BDNF regulates inhibitory synaptic transmission in the ventromedial nucleus of the hypothalamus. J. Neurophysiol. (2012) Jan; 107: 42-49 

F. REVIEWS AND CHAPTERS

1. Jo, YH and Chua S.C., The Brain–Liver Connection Between BDNF and Glucose Control. Diabetes, Vol 62: 1367-1368 (2013)

2. Jo, YH and Buettner, C., Why leptin keeps you warm. Molecular metabolism, Oct 1; 3(8):779-80 (2014)