Altered expression of inflammation-associated genes in the hypothalamus of obesity mouse models

Abstract

Metabolic inflammation is a distinct feature of obesity. Increased inflammation in the adipose tissue and the liver has been so far implicated to affect metabolic homeostasis, mainly insulin resistance. In addition to the peripherals, the inflammation in the hypothalamus which governs systemic metabolism by linking neuronal and endocrine signals has been suggested to be linked to the metabolic disease. However, the underlying molecular mechanisms are poorly understood. We hypothesized that a high-fat diet (HFD) led to central metabolic inflammation via transcriptional changes in the hypothalamus. To address the hypothesis, we characterized obesity-related hypothalamic, transcriptional alterations, and their effects on functional networks. Male C57BL/6J mice were fed with either a control diet (CD) or an HFD for 20 weeks. Microarray and gene ontology analyses of the hypothalamus demonstrated that immune-related pathways, including inflammatory and cytokine signaling, were overrepresented in the hypothalamus of HFD-fed mice compared to that of CD mice. In addition, through secondary analysis of leptin-deficient obese (ob/ob) mouse hypothalamus, we found that enriched gene sets for tumor necrosis factor-alpha signaling pathways and cancer pathways were common in both the obese mouse models. The results suggest that inflammatory pathway is transcriptionally enriched in the hypothalamus in obesity models and is related with hyperadiposity rather than the primary causes of obesity including the dietary fat and the genetic mutation. (C) 2018 Elsevier Inc. All rights reserved.