Fat hurts, and exercise helps, the brain.

Gretchen Reynolds points to work by Erion et al.. showing that in obese mice inflammatory cytokines released by fat tissue enter the brain and cause nerve inflammation in the hippocampus, leading to poor learning and memory skills. Apparently obesity weakens the blood-brain barrier that normally would prevent entry of the inflammatory cytokines. (Adipose tissue in obese humans also is a source of proinflammatory cytokines). The authors found that treadmill training could restore the cognitive deficits and normalize hippocampal synaptic function. The same result could be obtained by simply removing fat tissue through lipectomy. Introduction of excess fat tissue into normal animals caused central inflammation and decay in cognitive and synaptic function. Finally they found that a blocker of the interleukin-1 receptors in the hippocampus protected the hippocampus from inflammation. This work "supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes." Here is their technical abstract:

Adipose tissue is a known source of proinflammatory cytokines in obese humans and animal models, including the db/db mouse, in which obesity arises as a result of leptin receptor insensitivity. Inflammatory cytokines induce cognitive deficits across numerous conditions, but no studies have determined whether obesity-induced inflammation mediates synaptic dysfunction. To address this question, we used a treadmill training paradigm in which mice were exposed to daily training sessions or an immobile belt, with motivation achieved by delivery of compressed air on noncompliance. Treadmill training prevented hippocampal microgliosis, abolished expression of microglial activation markers, and also blocked the functional sensitization observed in isolated cells after ex vivo exposure to lipopolysaccharide. Reduced microglial reactivity with exercise was associated with reinstatement of hippocampus-dependent memory, reversal of deficits in long-term potentiation, and normalization of hippocampal dendritic spine density. Because treadmill training evokes broad responses not limited to the immune system, we next assessed whether directly manipulating adiposity through lipectomy and fat transplantation influences inflammation, cognition, and synaptic plasticity. Lipectomy prevents and fat transplantation promotes systemic and central inflammation, with associated alterations in cognitive and synaptic function. Levels of interleukin 1β (IL1β) emerged as a correlate of adiposity and cognitive impairment across both the treadmill and lipectomy studies, so we manipulated hippocampal IL1 signaling using intrahippocampal delivery of IL1 receptor antagonist (IL1ra). Intrahippocampal IL1ra prevented synaptic dysfunction, proinflammatory priming, and cognitive impairment. This pattern supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes.