Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system

Abstract

Obesity is associated with chronic low-grade inflammation in peripheral tissues caused, in part, by the recruitment of inflammatory monocytes into adipose tissue. Studies in rodent models have also shown increased inflammation in the central nervous system (CNS) during obesity. The goal of this study was to determine whether obesity is associated with recruitment of peripheral immune cells into the CNS. To do this we used a bone marrow chimerism model to track the entry of green-fluorescent protein (GFP) labeled peripheral immune cells into the CNS. Flow cytometry was used to quantify the number of GFP+ immune cells recruited into the CNS of mice fed a high-fat diet compared to standard chow fed controls. High-fat feeding resulted in obesity associated with a 30% increase in the number of GFP+ cells in the CNS compared to control mice. Greater than 80% of the GFP+ cells recruited to the CNS were also CD45+ CD11b+ indicating that the GFP+ cells displayed characteristics of microglia/macrophages. Immunohistochemistry further confirmed the increase in GFP+ cells in the CNS of the high-fat fed group and also indicated that 93% of the recruited cells were found in the parenchyma and had a stellate morphology. These findings indicate that peripheral immune cells can be recruited to the CNS in obesity and may contribute to the inflammatory response.

Short-Term High-Fat-and-Fructose Feeding Produces Insulin Signaling Alterations Accompanied by Neurite and Synaptic Reduction and Astroglial Activation in the Rat Hippocampus

“…One of the pathologic features of obesity and InsRes is inflammation, and it has been described that central inflammation has an impact on brain function possibly through the import of inflammatory cytokines and immune cells into the central nervous system. 31,[36][37][38] Consistent with these reports, we found a significant increase in reactive astrocyte number and size in the hippocampus of HFFD rats, as well as GFAP þ subgranular cells extending vertical processes onto the granular layer of the DG of what we believe, based on morphology and location, is radial glia. In addition, we found slight changes in some microglial cells consistent in increased body size suggesting the onset of a subtle microglial activation.…”

“…Given that inflammation and reactive astrogliosis have been found in the hypothalamus in response to obesity, 31 we wanted to evaluate the impact of a short-term exposure to HFFD feeding in astrocytic activation in the hippocampus using GFAP immunohistochemistry to evaluate the number and morphology of astrocytes. Diet-induced obesity was associated with a significant increase in GFAP þ cell number in CA1 (51%, Po0.001) and DG (25.69%, Po0.05) ( Figures 5A and B), accompanied by a significant increase in GFAP area in both CA1 (77.7% Po0.001) and DG (62.5%, Po0.05) ( Figure 5B).…”

Role of Adiposity-Driven Inflammation in Depressive Morbidity

“…Consistent with this, recent data highlight increased inflammatory processes in the brain of obese individuals (Buckman et al, 2013;Rummel et al, 2010). This is particularly notable in the hypothalamus, where clinical indication of glial activation has been reported (Thaler et al, 2012).…”

The initiation of metabolic inflammation in childhood obesity

“…Inflammation is observed in a range of tissues involved in nutrient control. For example, proinflammatory macrophage signatures are observed in sites that include adipose tissue, gut (93), liver (94), pancreas (95), muscle (96), and CNS (18,97). Animal models suggest that short-term HFD feeding leads to acute proinflammatory signals in the hypothalamus without significant leukocyte activation in other tissues that may be largely reversible (65).…”