Alessandro Bartolomucci, Ph.D.

Associate Professor, Department of Integrative Biology and Physiology

E-MAIL: [email protected]

Advising Statement

Research Interests:

VGF-derived peptides: biochemistry and role in obesity and diabetes

My laboratory has pioneered the research on VGFgene derived peptides with special reference to their role in obesity. We have identified a VGF peptide designated TLQP-21 in the rodent brain and later identified its expression in sympathetic nerve terminals innervating the adipose organ. We first established its unique role in energy homeostasis and peripheral pro-lipolytic effects. We also established that TLQP-21 activates the Complement 3a Receptor 1 (C3aR1) with a folding upon binding mechanism and that the C-terminal aminoacid arginine is the hot spot for the biological activity. Finally we demonstrated that the human version of TLQP-21 is less potent than the mouse version in activating the human C3aR1. We are currently characterizing the molecular mechanism of TLQP-21 anti-obesity and pro-lipolytic effect. The long term goal is to combine biological and chemical data to devise small molecular analogues having improved anti-obesity effects.

Stress, Obesity and Aging

My laboratory developed a unique naturalistic model of chronic social stress and established a social-rank-dependent vulnerability to psychopathogies, neurological abnormalities and obesity. Importantly we demonstrated that subordinate mice (mice having low social rank) manifest a complex syndrome characterized by a depression-like behavior, increased anxiety, neuroimmune and neuroendocrine abnormalities. Importantly, subordinate mice develop hyperphagia, a binge-eating disorder and are highly vulnerable to diet-induced obesity, metabolic-like syndrome and pre type 2-diabetes. Mechanistically the metabolic abnormalities are associated with impaired insulin signaling in metabolic tissues. We are currently investigating the role of the brown adipose tissue and the impact of adaptive thermogenesis on obesity/diabetes vulnerability and resiliency. We are also investigating the impact of chronic stress on senescence and ageing.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

  • Lyons CE, Razzoli M, Bartolomucci A. The impact of life stress on hallmarks of aging and accelerated senescence: connections in sickness and in health. Neurosci Biobehav Rev. 2023 Aug 14:105359. 
  • Sahu BS, Razzoli M, McGonigle S, Pallais JP, Nguyen ME, Sadahiro M, Jiang C, Lin WJ, Kelley KA, Rodriguez P, Mansk R, Cero C, Caviola G, Palanza P, Rao L, Beetch M, Alejandro E, Sham YY, Frontini A, Salton SR, Bartolomucci A. Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis. Mol Metab. 2023 Jul 21;76:101781. 
  • Razzoli M, Nyuyki-Dufe K, Chen BH, Bartolomucci A. Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress. Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2211755120.
  • Sahu BS, Nguyen ME, Rodriguez P, Pallais JP, Ghosh V, Razzoli M, Sham YY, Salton SR, Bartolomucci A. The molecular identity of the TLQP-21 peptide receptor. Cell Mol Life Sci. 2021 Dec;78(23):7133-7144.
  • Paterlini S, Panelli R, Gioiosa L, Parmigiani S, Franceschini P, Bertocchi I, Oberto A, Bartolomucci A, Eva C, Palanza P. Conditional inactivation of limbic neuropeptide Y-1 receptors increases vulnerability to diet-induced obesity in male mice. Int J Mol Sci. 2021 Aug 14;22(16):8745.
  • Lyons CE, Zhou X, Razzoli M, Chen M, Xia W, Ashe K, Zhang B, Bartolomucci A. Lifelong chronic psychosocial stress induces a proteomic signature of Alzheimer's Disease in wildtype mice. Eur J Neurosci. 2021 May 28. doi: 10.1111/ejn.15329.
  • Lyons CE, Bartolomucci A. Stress and Alzheimer's disease: A senescence link? Neurosci Biobehav Rev. 2020 Aug;115:285-298.
  • Razzoli M, Lindsay A, Law ML, Chamberlain CM, Southern WM, Berg M, Osborn J, Engeland WC, Metzger JM, Ervasti JM, Bartolomucci A. Social stress is lethal in the mdx model of Duchenne muscular dystrophy. EBioMedicine. 2020 Mar 3:102700.
  • Lyons CE, Razzoli M, Larson E, Svedberg D, Frontini A, Cinti S, Vulchanova L, Sanders M, Thomas M, Bartolomucci A. Optogenetic-induced sympathetic neuromodulation of brown adipose tissue thermogenesis.FASEB J. 2020;34(2):2765-2773.
  • Sahu BS, Rodriguez P, Nguyen ME, Han R, Cero C, Razzoli M, Piaggi P, Laskowski LJ, Pavlicev M, Muglia L, Mahata SK, O'Grady S, McCorvy JD, Baier LJ, Sham YY, Bartolomucci A. Peptide/receptor co-evolution explains the lipolytic function of the neuropeptide TLQP-21. Cell Rep. 2019;28(10):2567-2580.e6.
  • Strakova J, Kamdar F, Kulhanek D, Razzoli M, Garry DJ, Ervasti JM, Bartolomucci A, Townsend D. Integrative effects of dystrophin loss on metabolic function of the mdx mouse. Sci Rep. 2018 Sep 11;8(1):13624.
  • Guo Z, Sahu BS, He R, Finan B, Cero C, Verardi R, Razzoli M, Veglia G, Di Marchi RD, Miles JM, Bartolomucci A. Clearance kinetics of the VGF-derived neuropeptide TLQP-21. Neuropeptides. 2018;71:97-103.
  • Razzoli M, Nyuyki-Dufe K, Gurney A, Erickson C, McCallum J, Spielman N, Marzullo M, Patricelli J, Kurata M, Pope EA, Touma C, Palme R, Largaespada DA, Allison DB, Bartolomucci A. Social stress shortens lifespan in mice. Aging Cell. 2018 Aug;17(4):e12778.
  • Razzoli M, Emmett MJ, Lazar MA, Bartolomucci A. β-Adrenergic receptors control brown adipose UCP-1 tone and cold response without affecting its circadian rhythmicity. FASEB J. 2018;32:5640-5646.
  • Matsumura N, Zordoky BN, Robertson IM, Hamza SM, Parajuli N, Soltys CM, Beker DL, Grant MK, Razzoli M, Bartolomucci A, Dyck JRB.  Co-administration of resveratrol with doxorubicin in young mice attenuates detrimental late-occurring cardiovascular changes.  Cardiovasc Res. 2018 Mar 16;. PMID: 29566148
  • Sahu BS, Manna PT, Edgar JR, Antrobus R, Mahata SK, Bartolomucci A, Borner GH, Robinson MS. Role of clathrin in dense core vesicle biogenesis. Mol Biol Cell. 2017;28(20):2676-2685.
  • Razzoli M, Pearson C, Crow S, Bartolomucci A. Stress, overeating, and obesity: Insights from human studies and preclinical models. Neurosci Biobehav Rev. 2017;76(Pt A):154-162.
  • Cero C, Razzoli M, Han R, Sahu BS, Patricelli J, Guo Z, Zaidman NA, Miles JM, O'Grady SM, Bartolomucci A. The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis. Mol Metab. 2016;6(1):148-158.
  • Razzoli M, Bartolomucci A. The dichotomous effect of chronic stress on obesity. Trends Endocrinol Metab. 2016;27(7):504-515.
  • Dandapat A, Perrin BJ, Cabelka C, Razzoli M, Ervasti JM, Bartolomucci A, Lowe DA, Kyba M. High frequency hearing loss and hyperactivity in DUX4 transgenic mice. PLoS One. 2016 Mar 15;11(3):e0151467.
  • Sanghez V, Cubuk C, Sebastián-Leon P, Carobbio S, Dopazo J, Vidal-Puig A, Bartolomucci A. Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice. Stress. 2016;19(2):214-224.
  • Razzoli M, Frontini A, Gurney A, Mondini E, Cubuk C, Katz LS, Cero C, Bolan PJ, Dopazo J, Vidal-Puig A, Cinti S, Bartolomucci A. Stress-induced activation of the brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Mol Metab. 2015;5(1):19-33.
  • Petrocchi-Passerri P, Cero C, Cutarelli A, Frank C, Severini C, Bartolomucci A, Possenti R. The vgf-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis. J Mol Endocrinol. 2015;54(3):227-w39.
  • Sadashiro M, Erickson C, Lin W, Shin AC, Razzoli M, Fargali S, Jiang C, Gurney A, Kelley KA, Buettner C, Bartolomucci A*, Salton SR. Role of VGF-derived carboxy-terminal peptides in energy balance and reproduction: analysis of 'humanized' knockin mice expressing full length or truncated VGF. Endocrinology. 2015;156(5):1724-1738.
  • Razzoli M, McCallum J, Gurney A, Engeland WC, Bartolomucci A. Chronic stress aggravates glucose intolerance in leptin receptor deficient (db/db) mice. Genes Nutr. 2015 May;10(3):458
  • Razzoli M, Sanghez V, Bartolomucci A. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder. Front Nutr. 2015;1(30). pii: 00030.
  • Razzoli M, Sanghez V, Bartolomucci A. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder. Front Nutr. 2015;1(30). pii: 00030.
  • Cero C, Vostrikov V, Verardi R, Severini C, Gopinath T, Braun PD, Sassano MF, Gurney A, Roth BL, Vulchanova L, Possenti R, Veglia G, Bartolomucci A. The TLQP-21 peptide activates the G-protein-coupled receptor C3aR1 via a folding-upon-binding mechanism. Structure. 2014;22(12):1744-1753.

Current Graduate Students:

Carey Lyons (Neuroscience, University of Minnesota)

Picture of Alessandro Bartolomucci