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    Perfil de hormônios e lipídios circulantes em pacientes com lipodistrofia generalizada congênita em resposta à ingestão alimentar
    (Universidade Federal de São Paulo (UNIFESP), 2020-07-31) Araujo, Camilla Oliveira Duarte De [UNIFESP]; Ribeiro, Eliane Beraldi [UNIFESP]; Universidade Federal de São Paulo
    Patients with congenital generalized lipodystrophy (CGL) are not able to store lipids in the adipose tissue, which causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin levels, the hormone form that is active in acute food intake stimulation. Moreover, the consequences of the derangements of lipid metabolism on plasma lipids have not been fully examined. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. An obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects. Additionnaly, the plasma lipidomic profile of CGL patients, in comparison to eutrophic individuals, was evaluated at the fasted state and after the intake of a meal. Eutrophic controls (EUT, n=10), obese subjects (OB, n=10) and CGL (n=11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. Additional blood samples were collected at 30 and 60 minutes for ghrelin determinations. In the CGL patients and eutrophic controls, non-target lipidomics was performed by liquid chromatography–mass spectrometry. The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL and OB had shorter satiation times than EUT. The CGL patients also had lower satiety time and their sensation of hunger was less attenuated by the meal. Fasting acylated ghrelin levels were lower in CGL than in EUT. After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals. Regarding the lipidomic analysis, clear differences were detected between the groups. Several molecular species of fatty acyls, glycerolipids, glycerophospholipids, and sphyngolipids were altered in the CGL group. All the detected molecular species of fatty acyls were upregulated. Increments of several species of diacylglycerols and of one triacylglycerols species were also observed in the CGL group. Among the glycerophospholipids, we observed alterations of some glycerophosphoethanolamines and glycerophosphoserines species, and of one species of cardiolipins. Among the sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. The data indicate that CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after refeeding suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation. The alterations in the lipid profile of CGL patients indicate that, besides the direct impact of the impairment of TAGs synthesis and lipid droplets formation, the metabolism of complex lipids is also affected in CGL patients. The findings highlight the importance of a deeper comprehension of the role of specific lipid categories in the metabolic derangements present in CGL.