Alessandra Bartolomucci, Ph.D.

Assistant Professor, Integrative Biology/Physiology


Research Interests:

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

My laboratory has pioneered the research on Vgf gene 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.

Selected Publications:

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

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. MOLECULAR METABOLISM 2016;5:13-33.

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. JOURNAL OF MOLECULAR ENDOCRINOLOGY. 2015;54(3):227-39.

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):1724-38.
*co-senior and co-corresponding author.

Razzoli M, McCallum J, Gurney A, Engeland WC, Bartolomucci A. Chronic stress aggravates glucose intolerance in leptin receptor deficient (db/db) mice. GENES AND NUTRITION, 2015 10:8.

Razzoli M, Sanghez V, Bartolomucci A. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder. FRONTIERS IN NUTRITION. 2015;1:30.

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. 22:1744–1753.

Possenti R, Muccioli G, Petrocchi P, Cero C, Cabassi A, Vulchanova L, Riedl M, Manieri M, Frontini A, Giordano A, Cinti S, Govoni P, Graiani G, Quaini F, Ghe C, Bresciani E, Bulgarelli I, Torsello A, Locatelli V, Sanghez V, Larsen B, Petersen J, Palanza P, Parmigiani S, Moles A, Levi A, Bartolomucci A. Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. BIOCHEMICAL JOURNAL, 2012;441:511-22

Bartolomucci A, G. La Corte, R. Possenti, V. Locatelli, A.E. Rigamonti, A. Torsello, E. Bresciani, I. Bulgarelli, R. Rizzi, F. Pavone, F.R. D'Amato, G. Mignogna, A. Giorgi, M.E. Schininà, A.M. Rinaldi, G. Elia, C. Brancia, G.-L. Ferri, R. Conti, B. Ciani, T. Pascucci, G. Dell'Omo, E.E. Muller, A. Levi, A. Moles. TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCE USA 2006.103,14584-14589.

Research Interests:

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.

Additional Publications:

Razzoli M, Sanghez V, Bartolomucci A. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder. FRONTIERS IN NUTRITION. 2015;1:30.

Sanghez V, Razzoli M, Carobbio S, Campbell M, McCallum J, Cero C, Ceresini G, Cabassi A, Govoni P, Franceschini P, de Santis V, Gurney A, Ninkovic I, Parmigiani S, Palanza P, Vidal-Puig A, Bartolomucci A. Psychosocial stress induces hyperphagia and exacerbates diet-induced insulin resistance and the manifestations of the Metabolic Syndrome. PSYCHONEUROENDOCRINOLOGY 2013;38:2933-42.

Bertocchi I, Oberto A, Longo A, Mele P, Sabetta M, Bartolomucci A, Palanza P, Sprengel R, Eva C. Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCE USA. 2011;108:19395-400

Bartolomucci A, Carola V, Pascucci T, Pugliesi-Allegra S, Lesch KP, Parmigiani S, Palanza P, Gross C. Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice. DISEASE MODELS & MECHANISMS. 2010;3:459-70. Journal cover of the month.

Alessandra Bartolomucci