Obesity is a chronic metabolic disorder characterized by an excess of body fat. Obesity results from prolonged positive energy balance (i.e. energy intake exceeding energy expenditure). Because obesity may develop over many years in humans, only small imbalances in energy intake and expenditure are required. The cause of excessive positive energy balance in obesity has not been clearly defined. Nevertheless, key regulatory components reside in the hypothalamus, specifically in the arcuate nucleus (ARC).
The central melanocortin system within the ARC is made up of two distinct subsets of neurons that express either pro-opiomelanocortin (POMC) or agouti-related peptide (AgRP). These peptides regulate their downstream target sites via modulation of melanocortin receptor type 3 (MC3R) and melanocortin receptor type 4 (MC4R) activity. Although POMC neurons were long considered to be a single homogeneous entity, recent studies, including our own, support considerable heterogeneity among POMC neurons. In particular, there are at least two phenotypically distinct populations of POMC neurons in the ARC. We hypothesize that these phenotypic distinctions reflect important functional differences and that the interplay between the phenotypically distinct populations of POMC neurons is required for integration of peripheral and central signaling molecules, thus controlling the anorexigenic outcome of POMC neurons. Thus we are currently determining how novel interactions between distinct populations of POMC neurons contribute to the control of hypothalamic neurophysiology and the regulation of energy homeostasis. Our laboratory employs optogenetics, electrophysiology and transgenic animal models to explore the physiological functions of these novel interactionsat the cellular and whole body levels. Understanding POMC-POMC neuronal interactions will help elucidate the elementary hypothalamic microcircuits controlling feeding and energy expenditure. Hence, this understanding will be crucial as we seek to determine the underlying cellular pathogenesis of the ongoing epidemic of obesity.
Recent Publications (2012- present)
1. Jo, YH*, Endogenous BDNF regulates inhibitory synaptic transmission in the ventromedial nucleus of the hypothalamus. J. Neurophysiol. Jan; 107: 42‐49 (2012)
2. 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, May; 153(5):2408‐19 (2012)
3. 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. Jul 18;32(29):9870‐9877 (2012)
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, 32(6):844‐57 (2013)
5. 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, Vol. 8 (4), e60828 (2013)
6. 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. 4:1862 (2013)
7. 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, 23; 3(1):19‐28 (2013)
8. Lee DK, Jeong JH, Oh SH and Jo YH* Apelin‐13 enhances arcuate POMC neuron activity via inhibiting M‐current. PLOS One, Mar 17;10(3):e0119457 (2015)
9. 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. 26;6:6618. doi: 10.1038/ncomms7618 (2015)
10. 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, 11;4(6):483-92 (2015)
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)
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