Nutrient-sensing mechanisms provide a means whereby information about the metabolic state of the organism can be relayed to brain circuits controlling motivation. Mesolimbic dopamine (DA) neurons play a key role in mobilizing behaviour and are targeted by peripheral hormones controlling appetite and energy expenditure, such as leptin, ghrelin and GLP-1. Emerging findings suggest that neurons responding to endocrine signals can also detect fatty acids (FA). FA are essential building blocks for nerve cells but they can also have important signalling, metabolic and neuroimmune actions. Several lines of evidence implicate FA metabolism and partitioning in the brain as a nutrient sensor regulating energy homeostasis.

The type and quantity of fat consumed can be highly variable, leading to changes in the composition and amount of circulating and central FA. Dietary lipids can also affect the generation of FA synthesized and released by neural cells [1]. The biological impact of FA depends on their chemical structure. The monounsaturated FA oleate and the saturated FA palmitate are the most abundant long-chain FA in circulation and can exert different actions in the brain. Independent of changes in body weight, prolonged intake of saturated dietary fat (palm oil; enriched in palmitate) dampens mesolimbic DA function in rats while a monounsaturated high-fat diet (olive oil; containing mostly oleate) is protective [2]. Furthermore, excessive intake of saturated fat leading to obesity elicits anxiodepressive behaviour in a manner relying on neuroinflammatory responses in the nucleus accumbens (NAc) [3].

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD