Nayara Ariel da Silva Lisboa, Nina Bruna de Souza Mawandji, Júlia Martins Vieira, Anna Clara da Silva Kefner, Pietra Morellato Oliveira, Karolini Zuqui Nunes, Paulo Henrique Oliveira de Souza, Fabiano Kenji Haraguchi, Blanca Elena Guerrero Daboin, Maria Isabel Alonso-Vale, Andressa Bolsoni-Lopes
Palmitoleic acid enhances glucose uptake through coordinated regulation of GLUT1 and GLUT4 and contributes to improved metabolic function in human adipocytes and redox homeostasis in vWAT obtained from women with obesity and prediabetes. These findings identify 16:1n-7 as a bioactive lipid that modulates human adipose tissue function under metabolically compromised conditions, underscoring its role in the nutritional regulation of glucose metabolism and redox homeostasis.
PURPOSE: Obesity-associated dysfunction of visceral white adipose tissue (vWAT) is characterized by impaired glucose handling, altered adipokine secretion, and redox imbalance, contributing to metabolic deterioration. Palmitoleic acid (16:1n-7), a monounsaturated fatty acid, has been implicated in regulation of glucose and lipid metabolism in rodent and cellular models; however, its effects on human adipocytes under metabolically compromised conditions remain incompletely understood. Here, we investigated the effects of in vitro treatment with 16:1n-7 on glucose uptake and metabolism, adipokine secretion, and oxidative stress in isolated adipocytes and vWAT obtained from women with obesity and prediabetes.
METHODS: vWAT explants were treated in vitro with palmitoleic acid (16:1n-7) or palmitic acid (16:0) at 200 µM for 48 h. Glucose and lipid metabolism, adipokine secretion, and oxidative stress were evaluated.
RESULTS: 16:1n-7 increased basal and insulin-stimulated glucose uptake in association with upregulation of GLUT1 and GLUT4 expression and increased AMPKα protein content. In parallel, 16:1n-7 promoted coordinated changes in metabolic gene expression favoring glucose utilization and glyceroneogenesis rather than de novo lipogenesis, without changes in lipolytic activity, accompanied by increased citrate synthase and PPARG expression. Endocrine function was also modulated, as 16:1n-7 reduced resistin secretion without impairing adiponectin levels. Moreover, although lipid peroxidation remained unchanged, 16:1n-7 reduced protein oxidation and reactive oxygen species production, together with increased IDH2 and reduced NOS2 expression, supporting selective attenuation of oxidative stress.
CONCLUSION: Palmitoleic acid enhances glucose uptake through coordinated regulation of GLUT1 and GLUT4 and contributes to improved metabolic function in human adipocytes and redox homeostasis in vWAT obtained from women with obesity and prediabetes. These findings identify 16:1n-7 as a bioactive lipid that modulates human adipose tissue function under metabolically compromised conditions, underscoring its role in the nutritional regulation of glucose metabolism and redox homeostasis.