Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

Abstract

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

“…Fulfilling the dietary recommended intake (DRI) of each nutrient is basic for a proper development and health, and to complete all of the required biological functions, including reproduction. Furthermore, not covering the requirements for a particular nutrient may have deeper impact on the progeny, as it has been found for VK in different vertebrate species [ 49 , 175 ]. Knowledge on VK metabolites, metabolism, functions, and identification of suitable and accurate biomarkers is critical to identify the DRI for VK in vertebrates.…”

Maternal High Fat Diet Affects Offspring’s Vitamin K-Dependent Proteins Expression Levels

“…To our knowledge, this is the first study to determine the long-term effects of the maternal diet on the expression levels of VKDPs from the offspring in older age. This study extends the analysis of VKDPs previously made in 6 week old offspring [ 27 ], when the mice have just become sexually mature, into offspring of 30 weeks of age, to assess the longer term effects of a HF diet on VKDP expression. Previously, no correlations were found between OCN , Periostin , Gas6 , or Vkor and any of the body or bone parameters (listed in Tables 1 and 3 ) in 6 weeks old offspring [ 27 ].…”

“…This study extends the analysis of VKDPs previously made in 6 week old offspring [ 27 ], when the mice have just become sexually mature, into offspring of 30 weeks of age, to assess the longer term effects of a HF diet on VKDP expression. Previously, no correlations were found between OCN , Periostin , Gas6 , or Vkor and any of the body or bone parameters (listed in Tables 1 and 3 ) in 6 weeks old offspring [ 27 ]. Therefore, the correlations found with OCN , Periostin and Vkor , in the 30 week animals studied here, are a consequence of age.…”

“…Females were mated with separate males, and after confirmation of mating (presence of a vaginal plug) were individually housed and fed either a standard chow control (C, n = 5 dams) diet RM-1 (Special Diet Services, Witham, Essex, UK) or a high-fat (HF, n = 6 dams) diet (Special Diet Services diet 824053, Special Diet Services). We have used these diets in an earlier study [ 27 ]. These C or HF diets were continued throughout pregnancy and lactation until the offspring had been weaned at 3 weeks of age.…”

“…Previously we have assessed the effect of maternal and offspring high fat diet on VKD proteins in the aorta and bone from 6 week old mice [ 27 ]. The data presented in this study extends these studies with analysis performed in offspring at 30 weeks of age.…”