Research highlights effects of high-fat diets on behavior, brain plasticity, and fatty acid metabolism in rats
Study: From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats. Image Credit: beats1 / Shutterstock.com
A recent study published in ACS Chemical Neuroscience examines how a high-fat diet (HFD) modifies inhibitory control.
Impulsivity and inhibitory control
Inhibitory control refers to the ability to control or inhibit impulsive or compulsive reactions. Abnormally high impulsivity and compulsivity are characteristic features of several psychological conditions, including attention deficit hyperactive disorder (ADHD), obsessive-compulsive disorder (OCD), autism, and schizophrenia.
Impulsivity can be further classified as impulsive action, which refers to a deficit in the inhibition of motor activity, or impulsive choice, in which the individual prefers immediate gratification over more significant but delayed rewards. Additionally, reflection impulsivity describes a sensory experience that remains to be proved.
Inhibitory control often subsides during adolescence; however, it can be perpetuated by an individual’s diet, the use of illegal substances, and sports.
Diet and impulse control
Both HFDs and high-sugar diets (HSDs) increase impulsive behavior. Prior research suggests that HFDs may increase neuroinflammation, immune system activation, and activation of dopamine (DA) neurons in various pathways,s including the mesolimbic and frontostriatal circuits.
DA receptors 1 (DR1) and DR2 are located near cannabinoid receptors 1 (CB1) in the brain, which are involved in appetite regulation. Through this association, HFDs influence the striatum and brainstem.
Studies examining the effects of HFDs in adolescent rats have reported conflicting results. Nevertheless, the nucleus accumbens of the mesolimbic pathway stimulates rats to eat more fat, whereas D1R inhibition reduces fat intake.
Consuming a HFD over a period of three months increases CB1 activity in the prefrontal cortex, which weakens with continuing consumption. Brain-derived neurotrophic factor (BDNF) levels rise after one day of HFD intake, with the difference between sexes widening with increased exposure.
About the study
The aim of the current study was to identify associations between adolescent HFD exposure and deficient inhibitory control as adults. The marker for impulsivity was premature responses, whereas perseverative responses reflected compulsive behavior.
To this end, the effects of HFD were assessed from the 33rd postnatal day (PND) of Wistar laboratory rats to PND 77. A total of 40 rats were included in the study and randomized to receive either HFD or normal laboratory rat diet.
All rats were subjected to several tasks to evaluate behavioral differences, including variable delay to signal (VDS), five-choice serial reaction time task (5-CSRTT), delay discounting task (DDT), and rodent gambling task (rGT). At the end of the study period, the frontal cortex was isolated from rat brains for sequencing.
Stool samples obtained on PND 298 were also subjected to metabolomic and fatty acid composition analyses.
Study findings
Increased motor impulsiveness
Total session time decreased in all groups, which suggests that normal learning occurred.
During the training sessions, no change in premature or perseverative responses was observed, except due to the progress of sessions. Prematurity response rates exhibited a similar session effect.
The test sessions showed a strong increase in premature responses and a tendency towards more premature responses with six—and 12-second delays.
HFD exposure in adolescent rats increased premature responses as compared to other groups, thus suggesting that adolescents are more sensitive to motor impulsivity after HFD consumption.
Reduced cognitive impulsivity
Despite these observations, cognitive impulsivity did not change, which implies a varying impact of the diet on different types of impulsivity. HFD rats were less likely to take risks and had fewer premature responses.
Although higher motor impulsive behavior was reported in HFD rats, these rats made fewer impulsive decisions than the normal diet group. These differences may be attributed to the different methodologies used to assess this parameter, as well as the potential effects of the presence or absence of food deprivation.
Compulsivity unaltered
No alterations in compulsivity were observed, as reported in previous studies. However, increased perseverative responses have been observed when rats were allowed to eat fatty foods at will; therefore, additional research is needed to explain these associations.
Gene expression in frontal cortex
Genes in food-regulating brain circuits exhibited significant and long-term changes, such as in DRD1 for males. Endocannabinoid system genes were also changed in these circuits, which may affect food rewards in association with the DA system.
BDNF expression increased in males but decreased in females, along with deficits in inhibitory control. Thus, adolescent females consuming an HFD diet are more likely to develop impulsive behaviors over longer durations.
The HFD did not consistently lead to obesity, which excludes the potential role of obesity on impulse control. Likewise, no evidence of neuroinflammation was observed in the current study.
Fatty acid composition
Gut-level metabolism was affected by the HFD as fatty acid levels were higher, whereas glucose and glycerol levels were lower. Glucose may signal that the body has enough energy rather than simply providing fuel for cognitive processes.
No effect of HFD consumption on omega-3 FA levels was observed. Earlier studies have shown increased motor impulsivity and propensity to make risky decisions after HFD consumption by adolescents. Omega-3 supplementation reduced these types of ADHD-like behaviors.
Conclusions
Rats consuming an HFD during adolescence were less likely to inhibit impulsive behaviors over extended periods. Deficits in inhibitory control affect different subcomponents to differing extents, as HFD rats had higher motor impulsivity but unchanged cognitive impulsive behavior.
HFD consumption was associated with alterations in neuroplasticity, dopamine gene regulation, and gut metabolism. These findings emphasize the importance of future studies to determine the mechanisms involved in these associations.
Journal reference:
- Ruiz-Sobremazas, D., Abreu, A. C., Prados-Pardo, A., et al. (2024). From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats. ACS Chemical Neuroscience. doi:10.1021/acschemneuro.4c00297.