Our laboratory focuses on brain sites and substrates mediating energy balance, in obesity prone and obesity-resistant animal models. The goal of our laboratory is to understand brain mechanisms important in determining the popensity for obesity. These investigations involve study of neuropeptides that regulate feeding behavior and energy expenditure, including that related to physical activity. Our most recent focus is on the role of orexin, also known as hypocretin. Orexin is a recently identified neuropeptide predominantly located in the lateral hypothalamus that enhances feeding and physical activity, and which also modifies sleep/wake patterns. Our laboratory has shown that orexin elevates non-volitional low-level activity, which has an important impact on body weight control. We have also shown that this low level activity may be important in maintaing obesity resistance during aging. The techniques we use include stereotaxic surgery, immunohistochemistry, food intake measurements, physical activity chamber measurements, indirect calorimetry, body composition (EchoNMR) radioimmunoassay and molecular biology procedures, including RNA/DNA extraction, northern blots, slot blots, rtPCR, cDNA probe synthesis, random primer labeling, hybridization, densitometry and microarrays.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Mavanji V, Georgopoulos AP, Kotz CM. Orexin enhances neuronal synchronization in adult rat hypothalamic culture: A model to study hypothalamic function. J Neurophysiol. 2022 May 1;127(5):1221-1229.
- Grebenstein PE, Erickson P, Grace M, Kotz CM. Anatabine, nornicotine, and anabasine reduce weight gain and body fat through decreases in food intake and increases in physical activity. J Clin Med. 2022 Jan 18;11(3):481.
- Mavanji V, Pomonis B, Kotz CM. Orexin, serotonin, and energy balance. WIREs Mech Dis. 2022 Jan;14(1):e1536.
- Butsch WS, Hajduk A, Cardel MI, Donahoo WT, Kyle TK, Stanford FC, Zeltser LM, Kotz CM, Jastreboff AM. COVID-19 vaccines are effective in people with obesity: A position statement from The Obesity Society. Obesity (Silver Spring). 2021 Oct;29(10):1575-1579.
- Zhang D, Perrey DA, Decker AM, Langston TL, Mavanji V, Harris DL, Kotz CM, Zhang Y. Discovery of arylsulfonamides as dual orexin receptor agonists. J Med Chem. 2021 Jun 24;64(12):8806-8825.
- Klockars A, Levine AS, Head MA, Perez-Leighton CE, Kotz CM, Olszewski PK. Impact of gut and metabolic hormones on feeding reward. Compr Physiol. 2021 Feb 12;11(2):1425-1447.
- Stanojlovic M, Pallais JP, Kotz CM. Inhibition of orexin/hypocretin neurons ameliorates elevated physical activity and energy expenditure in the A53T mouse model of Parkinson's disease. Int J Mol Sci. 2021 Jan 14;22(2):795.
- Mavanji V, Georgopoulos AP, Kotz CM. Synchronous neuronal interactions in rat hypothalamic culture: a novel model for the study of network dynamics in metabolic disorders. Exp Brain Res. 2021 Mar;239(3):755-764.
- Stanojlovic M, Pallais JP, Lee MK, Kotz CM. Pharmacological and chemogenetic orexin/hypocretin intervention ameliorates Hipp-dependent memory impairment in the A53T mice model of Parkinson's disease. Mol Brain. 2019 Oct 30;12(1):87.
- Stanojlovic M, Pallais JP, Kotz CM. Chemogenetic modulation of orexin neurons reverses changes in anxiety and locomotor activity in the A53T mouse model of Parkinson's disease. Front Neurosci. 2019 Jul 30;13:702.
- Stanojlovic M, Pallais Yllescas JP Jr, Vijayakumar A, Kotz C. Early sociability and social memory impairment in the A53T mouse model of Parkinson's disease are ameliorated by chemogenetic modulation of orexin neuron activity. Mol Brain. 2019 Oct 30;12(1):87.
- Stanojlovic M, Pallais Yllescas JP Jr, Mavanji V, Kotz C. Chemogenetic activation of orexin/hypocretin neurons ameliorates aging-induced changes in behavior and energy expenditure. Am J Physiol Regul Integr Comp Physiol. 2019;316:R571-R583.
- Zink AN, Bunney PE, Holm AA, Billington CJ, Kotz CM. Neuromodulation of orexin neurons reduces diet-induced adiposity. Int J Obes (Lond). 2018;42(4):737-745.
- Mavanji V, Butterick TA, Duffy CM, Nixon JP, Billington CJ, Kotz CM. Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice. Neurobiol Learn Mem. 2017;146:21-30.
- Kotz CM, Perez-Leighton CE, Teske JA, Billington CJ. Spontaneous physical activity defends against obesity. Curr Obes Resp. 2017;6:362-370.
- Coborn JE, DePorter DP, Mavanji V, Sinton CM, Kotz CM, Billington CJ, Teske JA. Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure. Int J Obes (Lond). 2017;41:1256-1262.
- Bunney PE, Zink AN, Holm AA, Billington CJ, Kotz CM. Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet. Physiol Behav. 2017;176:139-148.
- Perez-Leighton C, Little MR, Grace M, Billington CJ, Kotz CM. Orexin signaling in rostral lateral hypothalamus and nucleus accumbens shell in the control of spontaneous physical activity in high- and low-activity rats. Am J Physiol Regul Integr Comp Physiol. 2017;312(3):R338-R346.
- Teske JA, Perez-Leighton C, Noble EE, Wang C, Billington CJ, Kotz CM. Effect of housing tuypes on growth, feeding, physical activity, and anxiety-like behavior in male Sprague-Dawley rats. Front Nutr. 2016 Feb 4;3:4. doi: 10.3389/fnut.2016.00004.
- Duffy CM, Yuan C, Wisdorf LE, Billington CJ, Kotz CM, Nixon JP, Butterick TA. Role of orexin A signaling in dietary palmitic acid-activated microglial cells. Neurosci Lett. 2015;606:140-144.
- Nixon JP, Mavanji V, Butterick TA, Billington CJ, Kotz CM, Teske JA. Sleep disorders, obesity, and aging: the role of orexin. Ageing Res Rev. 2015;20:63-73.
- Mavanji V, Perez-Leighton CE, Kotz CM, Billington CJ, Parthasarathy S, Sinton CM, Teske JA. Promotion of wakefulness and energy expenditure by orexin-A in the ventrolateral preoptic area. Sleep. 2015;38:1361-1370.
- Zink AN, Perez-Leighton CE, Kotz CM. The orexin neuropeptide system: physical activity and hypothalamic function throughout the aging process. Front Syst Neurosci. 2014;8:211.
- Noble EE, Billington CJ, Kotz CM, Wang C. Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. Am J Physiol Regul Integr Comp Physiol. 2014;307(6):R737-45.
- Perez-Leighton CE, Grace M, Billington CJ, Kotz CM. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats. Physiol Behav. 2014;135:104-11.
- Butterick TA, Duffy CM, Lee RE, Billington CJ, Kotz CM, Nixon JP. Use of a caspase multiplexing assay to determine apoptosis in a hypothalamic cell model. J Vis Exp. 2014 Apr 16;(86).
- Noble EE, Mavanji V, Little MR, Billington CJ, Kotz CM, Wang C. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons. Neurobiol Learn Mem. 2014;114C:40-50.
Former Graduate Students:
Anastasia Zink (Ph.D. 2015, Neuroscience, University of Minnesota).
Claudio Perez-Leighton (Ph.D. 2012, Neuroscience, University of Minnesota).
Erwin Ferri (M.S. 2009, Neuroscience, University of Minnesota).
Andrew Thorpe (Ph.D. 2004, Neuroscience, University of Minnesota).