Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage

Abstract

Introduction Saturated fatty acids (FAs) are the main component of high‐fat diets (HFDs), and high consumption has been associated with the development of insulin resistance, endoplasmic reticulum stress and mitochondrial dysfunction in neuronal cells. In particular, the reduction in neuronal insulin signaling seems to underlie the development of cognitive impairments and has been considered a risk factor for Alzheimer's disease (AD). Methods This review summarized and critically analyzed the research that has impacted the field of saturated FA metabolism in neurons. Results We reviewed the mechanisms for free FA transport from the systemic circulation to the brain and how they impact neuronal metabolism. Finally, we focused on the molecular and the physiopathological consequences of brain exposure to the most abundant FA in the HFD, palmitic acid (PA). Conclusion Understanding the mechanisms that lead to metabolic alterations in neurons induced by saturated FAs could help to develop several strategies for the prevention and treatment of cognitive impairment associated with insulin resistance, metabolic syndrome, or type II diabetes.

High-Fat Diets in Animal Models of Alzheimer’s Disease: How Can Eating Too Much Fat Increase Alzheimer’s Disease Risk?

“…SFA are carbon chains containing a methyl group on one end of its structure and a carboxyl group at the other end. SFA, by definition, do not present double bonds in their structure and can be classified into two broad categories: long-chain saturated fatty acids (LCFA) and short-chain fatty acids (SCFA), although this is not a standardized definition [40,41]. LCFA are typically found in dairy and red meat, but food sources contain a mixture of different fatty acids, which can influence their different physiological effects [40].…”

“…HFD may also promote central insulin resistance, which is detected in the brain itself in AD, particularly at the vascular level [157,159,202] and negatively affect neurovascular coupling and cerebrovascular function even in the absence of dyslipidemia [307]. These metabolic abnormalities would then induce alterations in neuronal morphology and physiology that translate in decreased long-term potentiation and reduced markers of synaptic plasticity [41]. Several lines of studies also suggest that HFD generate a proinflammatory environment, which may further favor A␤ deposition and tau phosphorylation and negatively affect synaptic plasticity [41,155,[308][309][310][311][312].…”

“…These metabolic abnormalities would then induce alterations in neuronal morphology and physiology that translate in decreased long-term potentiation and reduced markers of synaptic plasticity [41]. Several lines of studies also suggest that HFD generate a proinflammatory environment, which may further favor A␤ deposition and tau phosphorylation and negatively affect synaptic plasticity [41,155,[308][309][310][311][312]. Increased lipid peroxidation and reduced autophagy have also been reported in the brain of obese mice while mitochondrial regulators including SIRT3 and PGC1␣ are reduced by saturated fats and cholesterol consumption, which may promote the accumulation of neurotoxic proteins and lead to neuronal death [313][314][315][316].…”

Bioactive Compounds in Sea Buckthorn and their Efficacy in Preventing and Treating Metabolic Syndrome

“…Saturated fatty acids have also been shown to have a cholesterol-raising effect [29]. Excessive intake of long-chain saturated fatty acids can contribute to mitochondrial dysfunction [31], insulin resistance, decreased glycolysis, and endoplasmic reticulum stress [32]. There is also evidence that saturated fatty acids themselves may play a rather limited role in the development of metabolic syndrome [33].…”

Die Energiebilanz charakterisiert Adipositas, sie erklärt sie aber nicht und sie ermöglicht keine Strategien für eine nachhaltige Behandlung

“…Eine enterale Applikation gesättigter Fette war innerhalb von Tagen in der Lage eine hypothalamische Entzündung zu induzieren, während einfach-ungesättigte Fettsäuren diesen Effekt nicht zeigten [19]. Gesättigte Fettsäuren wie Palmitinsäure und Stearinsäure können die Blut-Hirn-Schranke überwinden und speziell im Hypothalamus akkumulieren, wo sie die anorexigene Signalwirkung von Insulin und Leptin abschwächen und dadurch eine positive Energiebilanz fördern (sieh hierzu [20][21][22]).…”