Intermittent Fasting Reduces Neuroinflammation and Cognitive Impairment in High-Fat Diet-Fed Mice by Downregulating Lipocalin-2 and Galectin-3

• Published in: Nutrients Vol. 16; no. 1; p. 159
• Main Authors: Lee, Jaewoong, An, Hyeong Seok, Shin, Hyun Joo, Jang, Hye Min, Im, Chae Oh, Jeong, Yeonjun, Eum, Kibaek, Yoon, Sejeong, Lee, So Jeong, Jeong, Eun Ae, Kim, Kyung Eun, Roh, Gu Seob
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-01-2024; MDPI
• Subjects: Adipocytes; Adipose tissues; Apoptosis; Body fat; Brain; Brain research; Cognitive ability; cognitive impairment; Diabetes; Diet; Enzymes; Fasting; galectin-3; Glucose; high-fat diet; Inflammation; Insulin resistance; intermittent fasting; lipocalin-2; Macrophages; Memory; Obesity; Permeability; Proteins; R&D; Research & development; Type 2 diabetes; Variance analysis; Japan; United States > US; Germany; cognitive impairment; intermittent fasting; lipocalin-2; galectin-3; high-fat diet
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16010159

Intermittent fasting (IF), an alternating pattern of dietary restriction, reduces obesity-induced insulin resistance and inflammation. However, the crosstalk between adipose tissue and the hippocampus in diabetic encephalopathy is not fully understood. Here, we investigated the protective effects of IF against neuroinflammation and cognitive impairment in high-fat diet(HFD)-fed mice. Histological analysis revealed that IF reduced crown-like structures and adipocyte apoptosis in the adipose tissue of HFD mice. In addition to circulating lipocalin-2 (LCN2) and galectin-3 (GAL3) levels, IF reduced HFD-induced increases in LCN2- and GAL3-positive macrophages in adipose tissue. IF also improved HFD-induced memory deficits by inhibiting blood-brain barrier breakdown and neuroinflammation. Furthermore, immunofluorescence showed that IF reduced HFD-induced astrocytic LCN2 and microglial GAL3 protein expression in the hippocampus of HFD mice. These findings indicate that HFD-induced adipocyte apoptosis and macrophage infiltration may play a critical role in glial activation and that IF reduces neuroinflammation and cognitive impairment by protecting against blood-brain barrier leakage.