Pioglitazone Improves the Maternal High Fructose Diet‐Impaired Glycolysis and Oxidative Phosphorylation of Astrocytes

Abstract

Accumulating reports suggest that cell metabolism in the offspring is disturbed by maternal nutritional insults, resulting in the development of metabolic diseases in the offspring. Our previous study further indicated that the spatial learning and memory is impaired in female offspring by maternal high fructose diet (HFD). However, the underlying mechanisms are largely unknown. Astrocytes, a non‐neuronal cell type in the brain known for metabolic support to neurons, elevate glycolysis and oxidative phosphorylation rates in response to energy demand arising from the high neuronal activity. In this study, we dissected the profiles of glycolysis and oxidative phosphorylation of hippocampal astrocytes obtained from female offspring of maternal regular diet (ND) and of maternal HFD. The results indicated that maternal HFD impaired astrocytic glycolysis, oxygen consumption rate and the activities of electron transport chain. Moreover, upregulation of p85 subunit of phosphatidylinositide 3‐kinases (PI3K), down‐regulation of glucose transporter 1 (GLUT1) and a decrease of glucose uptake were detected in the maternal HFD‐programmed astrocytes. An insulin sensitizer, pioglitazone, treatment effectively improved the impaired glycolysis and oxidative phosphorylation and enhanced the astrocytic ATP content. Moreover, the suppressions of GLUT1 and glucose uptake in the HFD group were reversed to the ND level. Together, these pieces of evidence suggested that maternal HFD during gestation and lactation impairs the astrocytic energy metabolism that can be normalized by promoting insulin signaling.Support or Funding InformationThis work was supported by grants from CMPRG8F0062 and CMRPG8E0263 to KLHW from the Chang Gung Memorial Hospital, Taiwan, Republic of China.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.