Licio Augusto Velloso

School of Medical Sciences – University of Campinas Laboratory of Cell Signaling The main objective of our group is to identify potential targets for the treatment of obesity. Most recent efforts are focused on the characterization of the cellular and molecular mechanisms involved in the abnormal control of food intake and energy expenditure by the hypothalamus. In 2005, we published the first evidence for a role of diet-induced hypothalamic inflammation as a determining event leading to a dysfunction of the hypothalamus in obesity. In 2009, we showed that TLR4 and endoplasmic reticulum stress are activated in the hypothalamus by dietary fats. Also, we were the first to report the increased rate of neuronal apoptosis in the hypothalamus of obese rodents. In 2011 we used functional magnetic resonance to provide the first evidence for a dysfunction of the hypothalamus of obese subjects. Currently, the lab is working in both human and animal studies searching for novel potential candidates for the development of therapeutic approaches for obesity.

TEAM

Technical staff

• Erika Anne de Freitas Robles Roman
• Gerson Júlio Nery Ferraz
• Joseane Morari

RESEARCH FELLOW

• Ana Carolina Marques
• Carina Solon da Silva
• Daiane Fátima Engel
• Guilherme Augusto da Silva Nogueira
• Milena Monfort Pires
• Thiago Matos Ferreira de Araújo

PHD

• Alexandre Moura Assis
• Davi Sidarta Vitória Rodrigues de Oliveira
• Letícia da Silva Pires
• Pedro Augusto Silva Nogueira
• Rodrigo Scarpari Carraro
• Rodrigo Stellzer Gaspar

MASTER

• Ariane Maria Zanesco
• Marcela Reymond Simões

SCIENTIFIC INITIATION

• Caio Fernando Biolcatti

MAIN DISCOVERIES

• Researchers at the Cell Signaling Laboratory demonstrated that the intake of diets rich in saturated fats promote damage to the hypothalamus – the brain region that controls hunger. Such damages are due to the activation of an inflammatory response. The persistence of this inflammation can lead to the death of neurons, making treatment even more difficult for this disease;
• The Cell Signaling Laboratory developed methods to study the function of the hypothalamus in human patients, which has helped create parallels between the disease in experimental models and in humans.

MAIN ARTICLES

a. Definition of GAD65 as the main autoantigen in type 1 diabetes. J Clin Invest 91: 2084, 1993. 137 citations b. Demonstration of molecular crosstalk between insulin and angiotensin II signaling pathways. PNAS 93: 12490, 1996. 473 citations c. Definition of in situ hypothalamic inflammation as an important mechanism involved in the hypothalamic dysfunction in obesity. Endocrinology 146: 4192, 2005. 1,105 citations d. Definition of UCP2 as a potential target for the treatment of type 2 diabetes mellitus. FASEB J 21: 1153, 2007. 104 citations e. Demonstration of neuronal apoptosis in the hypothalamus of animal models of obesity. PLoS One 4: e5045, 2009. 426 citations f. Identification of TLR4 as a triggering mechanism for hypothalamic inflammation in obesity. J Neurosci 29: 359, 2009. 1,007 citations g. Demonstration of hypothalamic dysfunction and partial reversibility in the hypothalamus of obese humans undergoing body mass loss. Diabetes 60: 1699, 2011. 128 citations h. Demonstration of the impact of a hypothalamic anti-inflammatory approach on the control of hepatic gluconeogenesis in obesity. Diabetes 61: 1455, 2012. 218 citations i. Use of bone marrow transplant to show that peripheral monocytes are required to perpetuate hypothalamic inflammation in obesity. Diabetes 63: 3770, 2014. 105 citations j. Use of bone marrow transplant to show the importance of TLR4 in cells derived from the bone marrow to mediate diet-induced insulin resistance. Endocrinology 156: 103, 2015. 51 citations k. Induction of hypothalamic neurogenesis by n-3 fatty acids. Diabetes 65: 673, 2016. 57 citations l. Expression and characterization of PUFA receptors in the hypothalamus: therapeutic implications regarding obesity. J. Neuroinflammation 14:91, 2017. 101 citations m. Demonstration that inhibition of the hypothalamic transcription factor IRX3 predisposes to obesity. EBioMed – Lancet 39:448, 2019. 28 citations n. Identification of IL10 as a modulator of brown adipose tissue structure and function. EBioMed – Lancet 39:436, 2019. 18 citations o. Demonstration that unsaturated fatty acids can activate thermogenesis through the brown adipose tissue. JCEM 106:472, 2021. 2 citations p. Identification of a hypothalamic transcription factor, NHLH2, that connects the control of food intake with behavior. J Neurosci 41:10004, 2021 2 citations