The orphan G protein-coupled receptor, GPR139, is expressed in the hypothalamus and is involved in the regulation of body mass, blood glucose, and insulin.

GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.

Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia.

Obesity is the major risk factor for several cardiovascular and metabolic disorders. Previous studies reported that deletion of Angiotensin II type 2 receptor (AT2R) protects against metabolic dysfunctions induced by high fat (HF) diet. However, the role of AT2R in obesity-induced cardiac hypertrophy remains unclear. Male AT2R knockout (AT2RKO) and wild type (AT2RWT) mice were fed with control or HF diet for 10 weeks. HF diet increased cardiac expression of AT2R in obese mice. Deletion of AT2R did not affect body weight gain, glucose intolerance and fat mass gain induced by HF feeding. However, loss of AT2R prevented HF diet-induced hypercholesterolemia and cardiac remodeling. Mechanistically, we found that pharmacological inhibition or knockdown of AT2R prevented leptin-induced cardiomyocyte hypertrophy in vitro. Collectively, our results suggest that AT2R is involved in obesity-induced cardiac hypertrophy.

Cardiorespiratory fitness in adolescents with obesity: a 6-month follow-up study / Aptidão Cardiorrespiratória em Adolescentes com obesidade: um estudo de seguimento de 6 meses

The aim of this study was to investigate whether the effects of a multidisciplinary intervention on cardiorespiratory fitness are maintained after 6-month follow-up in adolescents with obesity. One-hundred and seven adolescents with obe-sity were intentionally allocated in two groups: experimental or control. Adolescents in experimental group underwent a multidisciplinary intervention (supervised aerobic exercise, psychological, nutritional, and clinical counseling). Cardiorespiratory fitness (direct gas analysis), body composition (dual-energy-DXA), anthropometry and blood lipids were measured before intervention (baseline), at the end of the 24-week intervention (post-intervention) and six months after the end of the intervention (follow-up). Cardiorespiratory fitness reduced in control group with no changes in experimental group, and these differences were maintained in the follow-up assessment (control group: 24.2±4.4 ml.kg-1.min-1to 22.6±4.9 ml.kg-1.min-1; follow-up: 22.6±4.9 ml.kg-1.min-1 vs. experimental group: 28.0±4.0 ml.kg-1.min-1 to 29.7±4.0 ml.kg-1.min-1; follow-up: 28.9±5.7 ml.kg-1.min-1). Reductions in z-score body mass index (BMI) and increases HDL-C af-ter multidisciplinary intervention were maintained after a 6-month follow-up. In conclusion, the benefits of a multidisciplinary intervention on cardiorespiratory fitness, BMI and blood lipids are maintained after a 6-month follow-up. These findings indicate that multidisciplinary interventions produce long-term health consequences on cardiorespiratory fitness. Reinforcing the importance of lifestyle changes as a therapeutic approach for the treatment of obesity in adolescents.

O objetivo do presente estudo foi investigar se os efeitos da intervenção multidisciplinar sobre a aptidão cardiorrespiratória são mantidos após um período de segmento de 6 meses em adolescentes com obesidade. Cento e sete adolescentes com obesidade foram intencionalmente alocados em dois grupos: experimental e controle. Os adolescentes do grupo experimental foram submetidos a intervenção multidisciplinar composta por acompanhamento psicológico, nutricional, clínico e treinamento aeróbio. Aptidão cardiorrespiratória (análise de gases), composição corporal (DEXA), antropometria e perfil lipídico foram avaliados no momento basal, após 24 semanas de intervenção e 6 meses após (follow up). A aptidão cardiorrespiratória reduziu no grupo controle sem alterações no grupo experimental, mesmo após o período de 6 meses (controle: 24,2±4,4 ml.kg-1.min-1 para 22,6±4,9 ml.kg-1.min-1; follow-up: 22,6±4,9 ml.kg-1.min-1 vs. grupo experimental: 28,0±4,0 ml.kg-1.min-1 para 29.7±4.0 ml.kg-1.min-1; follow-up: 28,9±5,7 ml.kg-1.min-1). Redução no escore-z do índice de massa corporal (Z-IMC) e elevação do HDL-c verificadas após 24 semanas, foram mantidas após o período de segmento. Os resultados indicam que os efeitos da intervenção multidisciplinar são mantidos após 6 meses de seguimento. Estes achados sugerem que intervenções multidisciplinares podem produzir alterações benéficas de longo prazo na capacidade cardiorrespiratória.