Project Summary/Abstract
Prolonged consumption of a high saturated fat (SF) diet is known to cause brain inflammation, and has recently
been shown to impair dopamine neurotransmission similar to chronic drug use. Brain imaging studies show that
obesity gradually reduces dopamine neurotransmission, but mechanisms that drive these changes are not
known. A hallmark of SF-induced obesity is insulin resistance and chronic inflammation that impacts both the
brain and peripheral tissues. Insulin signaling is essential to fine tune dopamine neurotransmission and helps
trigger satiety circuits, but insulin signaling is weakened by pro-inflammatory cytokines. Cytokines are released
in the brain by immune cells called microglia and astrocytes, which can be directly triggered by SF. This project
seeks to identify whether these glial immune cells respond to SF in a way that increases inflammatory cytokines,
and whether the increase in cytokines alters dopamine neurotransmission alone or by interfering with insulin
signaling. Determining the role of glial cells in this process would provide a therapeutic target to normalize
dopamine neurotransmission in obesity, and restore normal satiety signals. We will also explore the effectiveness
of anti-inflammatory unsaturated fatty acids to reduce brain inflammation and restore dopamine
neurotransmission. We hypothesize that a diet enriched with flaxseed oil, a potent source of anti-inflammatory
omega 3 fatty acids, will attenuate the actions of pro-inflammatory cytokines (TNF-a, IL-6, and IL-1ß) induced by
the SF diet, improve insulin sensitivity, and restore deficits in dopamine neurotransmission after prolonged SF
intake. We will also test whether inflammation caused by saturated fat-induced obesity interferes with insulin-
induced satiety. Data collected from this project will demonstrate the efficacy of flaxseed oil to treat obesity-
related changes in dopamine neurotransmission, and will provide a novel treatment approach to prevent over-
eating. Ultimately, identifying the impact of inflammation of dopamine neurotransmission, and characterizing how
these changes in dopamine signaling interfere with satiety will help us understand how diet-induced obesity
leads to dysregulated food intake, promoting over-eating when physiological needs have been met.