Impact of obesity-associated diabetes mellitus on the development of hypothalamic gliosis in adolescents

• Grant number: 17/00657-0
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): December 01, 2017
• Effective date (End): November 30, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Leticia Esposito Sewaybricker
• Grantee: Leticia Esposito Sewaybricker
• Host Investigator: Ellen Anne Schur
• Host Institution: Fundação de Desenvolvimento da UNICAMP (FUNCAMP). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: University of Washington, United States

Abstract

In experimental diet-induced obesity, the hypothalamus is affected by an inflammatory response that disturbs the function of key neurons involved in the regulation of caloric intake and energy expenditure. Advances in neuroimaging and the use of a quantitative magnetic resonance imaging (MRI) allowed the detection of radiological signs of gliosis in the medial basal hypothalamus (MBH). In both animal models and adults with obesity this finding is directly related to a higher body mass index (BMI). Childhood obesity is a risk factor for obesity in adults as well as the development of comorbidities. Our recent study showed that radiological signs of hypothalamic gliosis are already present in obese children and adolescents and those signs are correlated to a higher percentage of abdominal body fat-the component of body fat that is more closely related to a high metabolic risk. Recent findings also show that hypothalamic gliosis in adults is associated with insulin resistance, independent of BMI. However, no previous study has verified whether changes in hypothalamic tissue characteristics are related to glucose metabolism in children. This study aims to assess if the early onset of diabetes or insulin resistance in children is related to hypothalamic gliosis development. For this, a quantitative MRI approach will be used to assess for the presence of MBH gliosis on 12 obese children with DM2, 12 obese without DM2, and 12 normal-weight participants. Fasting glucose and insulin levels, dietary recalls and level of physical activity will also be evaluated. This study may increase the knowledge on hypothalamic dysfunction in obesity and its relation to insulin resistance and body energy homeostasis. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JULIANO HENRIQUE BORGES; DANIELA ALBIERO CAMARGO; LETICIA ESPOSITO SEWAYBRICKER; RENATA ISA SANTORO; DANIEL MINUTTI DE OLIVEIRA; SOFIA HELENA VALENTE DE LEMOS-MARINI; BRUNO GELONEZE; GIL GUERRA-JÚNIOR; EZEQUIEL MOREIRA GONÇALVES. Normal ambulatory blood pressure in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy. ARCHIVES OF ENDOCRINOLOGY METABOLISM, 2022-08-12. (12/16778-8, 14/20186-4, 11/23460-1, 17/00657-0)

BORGES, JULIANO HENRIQUE; CAMARGO, DANIELA ALBIERO; SEWAYBRICKER, LETICIA ESPOSITO; SANTORO, RENATA ISA; DE OLIVEIRA, DANIEL MINUTTI; DE LEMOS-MARINI, SOFIA HELENA VALENTE; GELONEZE, BRUNO; GUERRA-JUNIOR, GIL; GONCALVES, EZEQUIEL MOREIRA. Normal ambulatory blood pressure in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 67, n. 1, p. 9-pg., 2023-01-01. (11/23460-1, 17/00657-0, 12/16778-8, 14/20186-4)

SEWAYBRICKER, LETICIA E.; MELHORN, SUSAN J.; ASKREN, MARY K.; WEBB, MARY F.; TYAGI, VIDHI; DE LEON, MARY ROSALYNN B.; GRABOWSKI, THOMAS J.; SEELEY, WILLIAM W.; SCHUR, ELLEN A.. Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis. International Journal of Obesity, v. 44, n. 1, p. 167-177, JAN 2020. (17/00657-0)

SEWAYBRICKER, LETICIA E.; MELHORN, SUSAN J.; PAPANTONI, AFRODITI; WEBB, MARY F.; HUA, JUN; ROTH, CHRISTIAN L.; CARNELL, SUSAN; SCHUR, ELLEN A.. Pilot multi-site and reproducibility study of hypothalamic gliosis in children. PEDIATRIC OBESITY, v. 16, n. 4, APR 2021. (17/00657-0)

SEWAYBRICKER, LETICIA ESPOSITO; MELHORN, SUSAN J.; ASKREN, MARY K.; WEBB, MARY; TYAGI, VIDHI; DE LEON, MARY ROSALYNN; GRABOWSKI, THOMAS J.; SCHUR, ELLEN. Impact of Insulin Resistance on Response to a Meal by Salience, Executive Control, and Default Mode Resting State Networks in Humans. Diabetes, v. 68, p. 2-pg., 2019-06-01. (17/00657-0)