Switching Adolescent High-Fat Diet to Adult Control Diet Restores Neurocognitive Alterations

Abstract

In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala) and for the hypothalamic-pituitary-adrenal (HPA) stress axis, which is required for cognitive and emotional processing. We recently demonstrated that adolescent, but not adult, high-fat diet (HF) exposure leads to impaired hippocampal function and enhanced amygdala function through HPA axis alteration (Boitard et al., 2012, 2014, 2015). Here, we assessed whether the effects of adolescent HF consumption on brain function are permanent or reversible. After adolescent exposure to HF, switching to a standard control diet restored levels of hippocampal neurogenesis and normalized enhanced HPA axis reactivity, amygdala activity and avoidance memory. Therefore, while the adolescent period is highly vulnerable to the deleterious effects of diet-induced obesity, adult exposure to a standard diet appears sufficient to reverse alterations of brain function.

Chemogenetic silencing of hippocampus and amygdala reveals a double dissociation in periadolescent obesogenic diet-induced memory alterations

“…Week 0, p = 0.99; Week 6 and 12 all p < 0.001; Table 1) as previously reported (Boitard et al, 2012(Boitard et al, , 2014(Boitard et al, , 2015(Boitard et al, , 2016.…”

“…However, the long-term aversion memory was differently impacted by periadolescent HFD and chemogenetic inhibition of the vHPC or the BLA during the odor-malaise pairing (Figure 4C; one-way ANOVA Group F 4,57 = 3.9, p = 0.007). As previously observed (Boitard et al, 2015(Boitard et al, , 2016, periadolescent HFD exposure induced a stronger aversion memory compared to the control CD group (p = 0.05, Dunnett's post hoc test). However, the relative consumption of odorized water of CNO-treated HFD groups is similar to the CD one (all p > 0.2, 13 Dunnett's post hoc test).…”

“…Given that childhood and adolescence are crucial periods for cognitive and brain development (Spear, 2000), they represent a window of vulnerability to external insults such as the deleterious impact of various diets (for reviews see Andersen, 2003;Noble & Kanoski, 2016;Reichelt & Rank, 2017). In rodents, we recently showed that periadolescent high-fat diet (HFD), from weaning to adulthood (covering adolescence) induced complex motivational (Naneix et al, 2017;Tantot et al, 2017) and memory deficits (Boitard et al, 2012(Boitard et al, , 2014(Boitard et al, , 2015(Boitard et al, , 2016Khazen et al, 2019). Importantly, we found that periadolescent, but not adult, HFD alters relational and spatial memories but enhances emotional memories (for reviews see Del Olmo & Ruiz-Gayo, 2018;Morin et al, 2017;Murray & Chen, 2019).…”

“…Here we investigated the causal role of ventral hippocampus (vHPC) and the basolateral amygdala (BLA) in memory deficits induced by periadolescent HFD. We previously assessed spatial and relational memory using aversive (Boitard et al, 2014(Boitard et al, , 2016 or rewarded (Boitard et al, 2012) learning tasks.…”

High-Fat Diet-Induced Obesity Causes Sex-Specific Deficits in Adult Hippocampal Neurogenesis in Mice

“…Evidence suggests that detrimental diet effects may be reversible, as switching from the high-fat to the control diet is capable of restoring neurogenesis in rodents; however, this study was performed in male rats only (Boitard et al, 2016). Interventions that improve metabolic outcomes, such as physical exercise and caloric restriction, promote neurogenesis and gliogenesis, increase growth factors and synaptic plasticity in the hippocampus, and improve cognitive performance (Lee et al, 2002;Bondolfi et al, 2004;Park and Lee, 2011;Kaptan et al, 2015;Chatterjee et al, 2016;Klein et al, 2016).…”