Young-Hwan Jo, Ph.D.

My research focuses on exploring the neurobiology of energy metabolism. First, my ongoing research examines whether liver-derived interoceptive signals can influence hepatic lipid metabolism and emotions. Proper integration and transportation of interoceptive signals from organs to the brain via vagal sensory neurons appear to be critical for psychological experiences ranging from various feelings and emotions to motivations and adaptive behaviors. Optimal sensing and integration of internal body signals are crucial for many essential physiological functions. I specifically seek to determine if there is a specialized anatomical organization of liver-innervating vagal sensory neurons and determine the roles of liver-projecting vagal sensory neurons in controlling hepatic lipid metabolism and emotions. This research area is novel and remains to be explored.

Second, I seek to define the role of the parasympathetic nervous system of the liver in controlling energy metabolism and hepatic steatosis. This research uses a unique, coordinated, and multidisciplinary combination of state-of-the-art techniques to identify and characterize the roles of parasympathetic cholinergic innervation in the control of hepatic metabolism in lean and obese mice. The methodologies used include viral tracing, virus-mediated gene delivery, in vivo fiber photometry, single-nucleus RNA-sequencing, spatial transcriptomics, and functional readouts of liver function.

Lastly, my study aims to assess the role of central melanocortin tone in the function of hypothalamic pro-opiomelanocortin (POMC) neurons projecting to the medial amygdala and the dorsal motor nucleus of the vagus in mice. The main objective of this study is to generate significant and applicable findings that illustrate the importance of both alpha-melanocyte-stimulating hormone and beta-endorphin in hypothalamic POMC neurons are critical in affecting the ability of hypothalamic POMC neurons to regulate energy balance, insulin resistance, and hepatic steatosis in obese mice.

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)

2. Hwang, JY, Okada, J, Liu, L, Pessin, JE, Schwartz, GJ, and Jo, Y.H. (2024) The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet. Plos Biol. 22 (11): e3002865; PMID: 39436946

3. Hwang, JY, Lee, SB, Okada, J, Liu, L, Pessin, JE, Chua, SC, Schwartz, GJ, and Jo, YH (2025), Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. Nature Commun., 16, 991, doi.org/10.1038/s41467-025-56328-5; PMID: 39856118

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)