Metabolic factors in the regulation of hypothalamic innate immune responses in obesity

• Published in: Experimental & molecular medicine Vol. 54; no. 4; pp. 393 - 402
• Main Authors: Folick, Andrew, Cheang, Rachel T., Valdearcos, Martin, Koliwad, Suneil K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2022; Springer Nature B.V; 생화학분자생물학회
• Subjects: 14/63; 38/91; 42/35; 42/41; 45/91; 59/57; 631/250/2504/342/1952; 631/378/1488/1562; 631/378/371; 64/60; 692/163/2743/2037; 692/163/2743/393; 96/106; 96/21; 96/63; Biomedical and Life Sciences; Biomedicine; Body weight; Body weight gain; Diet, High-Fat - adverse effects; Drug development; Energy balance; Energy Metabolism; Food intake; High fat diet; Homeostasis; Humans; Hypothalamus; Hypothalamus - metabolism; Immune response; Immunity, Innate; Immunosuppressive agents; Inflammation; Innate immunity; Medical Biochemistry; Metabolic disorders; Metabolism; Microbiomes; Microglia; Microglia - metabolism; Molecular Medicine; Neurological diseases; Neuronal-glial interactions; Neurons; Obesity; Obesity - metabolism; Parenchyma; Review; Review Article; Stem Cells; Therapeutic targets; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-021-00666-z

The hypothalamus is a central regulator of body weight and energy homeostasis. There is increasing evidence that innate immune activation in the mediobasal hypothalamus (MBH) is a key element in the pathogenesis of diet-induced obesity. Microglia, the resident immune cells in the brain parenchyma, have been shown to play roles in diverse aspects of brain function, including circuit refinement and synaptic pruning. As such, microglia have also been implicated in the development and progression of neurological diseases. Microglia express receptors for and are responsive to a wide variety of nutritional, hormonal, and immunological signals that modulate their distinct functions across different brain regions. We showed that microglia within the MBH sense and respond to a high-fat diet and regulate the function of hypothalamic neurons to promote food intake and obesity. Neurons, glia, and immune cells within the MBH are positioned to sense and respond to circulating signals that regulate their capacity to coordinate aspects of systemic energy metabolism. Here, we review the current knowledge of how these peripheral signals modulate the innate immune response in the MBH and enable microglia to regulate metabolic control. Obesity: The role of immune cells in the brain Immune cells in the brain that contribute to metabolic dysfunction could offer a therapeutic target for treating obesity. In a review article, a team led by Martin Valdearcos and Suneil Koliwad from the University of California, San Francisco, USA, discuss the evidence linking microglia and other immune cells found in the brain’s hypothalamus region to the regulation of food intake and weight gain. The researchers describe how hormones, inflammatory molecules, nutrients, and microbiome-derived factors can all impact microglia in ways that affect how the immune cells interact with the neurons responsible for metabolic control. Although much remains to be learned about which aspects of microglial function are integral to obesity promotion, the authors argue that, in principle, drugs that target these immune cells could help combat excess weight gain and related metabolic disorders.