A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring.
Methyl deficiencies have been implicated in metabolic programming during the periods of oocyte and embryo development. Semisynthetic methyl-deficient diets (MD) with no folic acid, 0.05% choline, and approximately one-half the recommended content of methionine were fed to female rats for 3 wk prior to mating and for the first 5 d of gestation. During the period of MD feeding, plasma homocysteine concentrations were approximately twice those of rats fed the complete (CON) diet. From d 5, both groups received a complete semipurified AIN diet until birth. On d 8, plasma homocysteine concentrations did not differ between the 2 groups. Thereafter, dams and offspring were fed a nonpurified diet for the remainder of the experiment. At 6 mo of age, the homeostatic model assessment (HOMA) index of the male MD offspring tended to be 32% higher (P = 0.053) and peak insulin during an oral glucose tolerance test (oGTT) was 39% higher (P < 0.05) compared with the male CON offspring. There was no difference in the response to an oGTT in the female offspring at 6 mo of age. The increased HOMA index of male MD offspring persisted to 12 mo of age. The peak glucose concentration during oGTT was 23% higher (P < 0.05) in MD compared with the CON males despite 39% greater (P < 0.05) peak insulin concentrations. This study shows that in rats, a physiologically relevant methyl-deficient diet fed during the period of oocyte maturation and preimplantation development programs gender-specific changes in glucose handling by the offspring.
The University of Aberdeen, Rowett Institute of Nutrition and Health, Bucksburn, Aberdeen, AB21 9SB, Scotland.
Christopher A
CA
Maloney
Susan M
SM
Hay
Loraine E
LE
Young
Kevin D
KD
Sinclair
William D
WD
Rees
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002796:Choline Deficiency / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006710:Homocysteine / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D008745:Methylation; D009752:Nutritional Status; D051381:Rats; D012727:Sex Characteristics
D001786:Blood Glucose; D007328:Insulin; D006710:Homocysteine; D005947:Glucose