Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats

Abstract

Maintaining cholesterol homeostasis in the brain is vital for its proper functioning. While it is well documented that dietary restriction modulates the metabolism of cholesterol peripherally, little is known as to how it can affect cholesterol metabolism in the brain. The present study was designed to elucidate the impact of long-term dietary restriction on brain cholesterol metabolism. Three-month-old male Wistar rats were exposed to long-term dietary restriction until 12 and 24 months of age. The concentrations of cholesterol, its precursors and metabolites, and food-derived phytosterols were measured in the serum, cortex, and hippocampus by gas chromatography/mass spectrometry. Relative changes in the levels of proteins involved in cholesterol synthesis, transport, and degradation were determined by Western blot analysis. Reduced food intake influenced the expression patterns of proteins implicated in cholesterol metabolism in the brain in a region-specific manner. Dietary restriction decreased the concentrations of cholesterol precursors, lanosterol in the cortex, and lanosterol and lathosterol in the hippocampus at 12 months, while the level of desmosterol was elevated in the hippocampus at 24 months. The concentrations of cholesterol and 24(S)-hydroxycholesterol remained unaffected. Food-derived phytosterols were significantly lower after dietary restriction in both the cortex and hippocampus at 12 and 24 months. These findings provide new insight into the effects of dietary restriction on cholesterol metabolism in the brain, lending further support to its neuroprotective effect.

Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging

“…In the aged rats LDF triggered the decrease in both the lano-and lathosterol concentrations in the hippocampus (20 and 20%, respectively). Interestingly, the only change following IF was an increase (37%) in desmosterol concentration in the hippocampus of aged rats (as we previously reported in Smiljanic et al 2014) while other metabolites remained unaltered ( Fig. 4c).…”

“…Although the overall cholesterol content remains stable following different dietary manipulations (Pallottini et al 2003;Mulas et al 2005;Hayakawa et al 2007;Fon Tacer et al 2010;Smiljanic et al 2014), a significant decrease in the levels of cholesterol precursors was detected even after short-term fasting (20 h) (Fon Tacer et al 2010). Similarly, we have shown that cholesterol content remained unchanged in the brain following both LDF and IF.…”

“…This change could point to the ability of IF to promote an age-related adaptive mechanism. The fact that desmosterol is a direct cholesterol precursor produced in the Bloch cholesterol synthesis pathway prevailing in young individuals (Lütjohann et al 2002) suggests a switch to a less energy-consuming synthesis pathway in the old animals exposed to IF (Smiljanic et al 2014). Thus, IF, but not LDF had the potency to promote energy-saving mechanism in the hippocampus.…”

“…To this end, we analyzed expression patterns of glucose transporters, GLUT1, GLUT3 and GLUT4, and AMPK and pAMPK in the cortex and hippocampus of both age groups. We also expanded our previously published data showing that IF affected the cholesterol metabolism in the aging brain (Smiljanic et al 2014), with the analyses of the effects of LDF on the concentration of cholesterol and its metabolites in the brain during aging.…”

Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat

“…Among those, we and others have reported that DR promotes neurogenesis [29], enhances plasticity [30,31], and retards ageassociated brain functional impairments [32][33][34]. The exceptionally diverse anti-aging and neuroprotective properties of DR are probably linked to its ability to recruit adaptive cellular stress responses and to modulate the neuroendocrine system both of which are impaired in aged animals.…”