Licio Augusto Velloso

Faculdade de Ciências Médicas – Universidade Estadual de Campinas

Laboratório de Sinalização Celular

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.

EQUIPE

Servidores Docentes

• Eliana Pereira de Araújo
• Licio Augusto Velloso

Servidores Técnicos Administrativos

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

Pesquisadores

• Carlos Henrique Grossi Sponton
• Natália Ferreira Mendes

Pós-doutorandos

• Bruna Bombassaro
• Gabriela Batitucci Miranda
• Guilherme Augusto Silva Nogueira
• Letícia da Silva Pires Canevare
• Vanessa de Oliveira Furino

doutorandos

• Ana Cristina Christovam
• Ana Carolina Gomes
• Ana Luísa Gallo Ferraz
• Ariane Zanesco
• Bruno Loyola Barbosa
• Carlos Eduardo Leher
• Ester Alves
• Flávia Caroline Gan
• Fernando Bladimir Valdivieso Rivera
• Gabriel Calheiros Antunes
• Lara Regina Ferreira
• Larissa Silva Bergantini
• Marcela Reymond Simões
• Maria Eduarda Martelli
• Natalia Stinghen Tonet
• Tatiane Ramos dos Santos Silveira

MeSTRandos

• Carolina Namie Sato Cortezão
• Felipe Adolpho Silvano
• Jéssica Jacinto
• Júlia Moreira da Silva
• Nicolly Porto Marin

iniciação científica

• Ana Laura de Oliveira Carvalho
• Bryan Durval
• Daniel Silva Júnior
• Doriel Ferreira de Jesus Alves
• Gabriely Amanda Cremasco
• Giovanna Ariozi dos Santos
• Igor Vinícius Cavalheiro
• Louise Buolnalumi Tácito Yogar

Estagiária

• Nayra Fernanda de Oliveira

PRINCIPAIS DESCOBERTAS

• 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.

PRINCIPAIS ARTIGOS 

1. Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression. J Clin Invest 91: 2084, 1993. 149 citations

2. Cross-talk between the insulin and angiotensin signaling systems. PNAS 93: 12490, 1996. 492 citations

3. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146: 4192, 2005. 1374 citations

4. Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action. FASEB J 21: 1153, 2007. 117 citations

5. High-fat diet induces apoptosis of hypothalamic neurons. PLoS One 4: e5045, 2009. 516 citations

6. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 29: 359, 2009. 1267 citations

7. Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects. Diabetes 60: 1699, 2011. 161 citations

8. Inhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver. Diabetes 61: 1455, 2012. 249 citations

9. Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes 63: 3770, 2014. 149 citations

10. TLR4 expression in bone marrow-derived cells is both necessary and sufficient to produce the insulin resistance phenotype in diet-induced obesity. Endocrinology 156: 103, 2015. 54 citations

11. n-3 Fatty Acids Induce Neurogenesis of Predominantly POMC-Expressing Cells in the Hypothalamus. Diabetes 65: 673, 2016. 73 citations

12. Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation. J. Neuroinflammation 14:91, 2017. 152 citations

13. The partial inhibition of hypothalamic IRX3 exacerbates obesity. EBioMed – Lancet 39:448, 2019. 45 citations

14. Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency. EBioMed – Lancet 39:436, 2019. 36 citations

15. Short Dietary Intervention with Olive Oil Increases Brown Adipose Tissue Activity in Lean but not Overweight Subjects. JCEM 106:472, 2021. 15 citations

16. Arcuate Nucleus Overexpression of NHLH2 Reduces Body Mass and Attenuates Obesity-Associated Anxiety/Depression-like Behavior. J Neurosci 41:10004, 2021. 13 citations