TY - JOUR
T1 - Conserved and differential effects of dietary energy intake on the hippocampal transcriptomes of females and males
AU - Martin, Bronwen
AU - Pearson, Michele
AU - Brenneman, Randall
AU - Golden, Erin
AU - Keselman, Alex
AU - Iyun, Titilola
AU - Carlson, Olga D.
AU - Egan, Josephine M.
AU - Becker, Kevin G.
AU - Wood, William
AU - Prabhu, Vinayakumar
AU - de Cabo, Rafael
AU - Maudsley, Stuart
AU - Mattson, Mark P.
PY - 2008/11/11
Y1 - 2008/11/11
N2 - The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of the males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on etheir ad libitum (control), 20% caloric restriction (CR), 40% CR, intermitten fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1α mTor pathways in both sexes. If down-regulated many genes in males including those involve in protein degradation and apoptosis, but up-regulated many genes females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral resposes of males and females to differences in energy availability.
AB - The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of the males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on etheir ad libitum (control), 20% caloric restriction (CR), 40% CR, intermitten fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1α mTor pathways in both sexes. If down-regulated many genes in males including those involve in protein degradation and apoptosis, but up-regulated many genes females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral resposes of males and females to differences in energy availability.
UR - http://www.scopus.com/inward/record.url?scp=48749115011&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0002398
DO - 10.1371/journal.pone.0002398
M3 - Article
C2 - 18545695
AN - SCOPUS:48749115011
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 6
M1 - e2398
ER -