Maternal Dietary Vitamin D Does Not Program Systemic Inflammation and Bone Health in Adult Female Mice Fed an Obesogenic Diet

Abstract

Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and bone structure in male offspring fed an obesogenic diet. Here we assessed if this effect is also apparent in females. C57BL/6J dams were fed AIN93G diet with high (5000 IU/kg diet) or low (25 IU/kg diet) vitamin D during pregnancy and lactation. Post-weaning, female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet (44.2% fat, 19.8% sucrose) until age seven months when glucose response, adiposity, serum LPS, and bone mineral, trabecular and cortical structure, and biomechanical strength properties of femur and vertebra were assessed. There was no evidence for a programming effect of vitamin D for any outcomes. However, females exposed to a high vitamin D diet post-weaning had higher bone mineral content (p = 0.037) and density (p = 0.015) of lumbar vertebra. This post-weaning benefit suggests that in females, bone mineral accrual but not bone structure is compromised with low vitamin D status in utero until weaning in an obesogenic context.

Bone development in growing female mice fed calcium and vitamin D at lower levels than is present in the AIN-93G reference diet

“…We have previously demonstrated that there is a window of opportunity during early life for novel food components, such as soy isoflavones, to favourably program bone outcomes at early adulthood in terms of higher BMD and improved bone structure and bone strength in female mice ( Kaludjerovic and Ward, 2010 ; Dinsdale et al, 2012 ; Kaludjerovic and Ward, 2009 ; Kaludjerovic and Ward, 2015 ). While these studies have used the AIN-93G reference diet that is recommended for supporting growth, pregnancy and lactation, the levels of vitamin D (vit D, 1000 IU/kg) and calcium (Ca, 5 g/kg) in this diet may be higher than required for normal bone development, measured as BMD and bone structure in mice and rats ( Glenn et al, 2014 ; Villa et al, 2016 ; Hunt et al, 2008 ). Findings from our group have demonstrated that normal bone development, measured as BMD and biomechanical bone strength, occurs with a significantly lower level of vit D (25 IU/kg) in mice fed an obesogenic diet, in inflammatory prone female mice or in healthy male mice ( Glenn et al, 2014 ; Villa et al, 2016 ; Jahani et al, 2014 ).…”

“…While these studies have used the AIN-93G reference diet that is recommended for supporting growth, pregnancy and lactation, the levels of vitamin D (vit D, 1000 IU/kg) and calcium (Ca, 5 g/kg) in this diet may be higher than required for normal bone development, measured as BMD and bone structure in mice and rats ( Glenn et al, 2014 ; Villa et al, 2016 ; Hunt et al, 2008 ). Findings from our group have demonstrated that normal bone development, measured as BMD and biomechanical bone strength, occurs with a significantly lower level of vit D (25 IU/kg) in mice fed an obesogenic diet, in inflammatory prone female mice or in healthy male mice ( Glenn et al, 2014 ; Villa et al, 2016 ; Jahani et al, 2014 ). In these studies, dietary Ca was kept constant at 5 g/kg and diets were fed from weaning until 3 ( Glenn et al, 2014 ; Jahani et al, 2014 ) or 7 months of age ( Villa et al, 2016 ).…”

Nutritional Programming of Bone Structure in Male Offspring by Maternal Consumption of Citrus Flavanones

“…These findings prompt the question of whether male siblings may experience similar detriments to BMD and bone structure. Sex-specific nutritional programming effects on the skeletal health of rodents have been observed using other food bioactives [ 3 , 6 , 10 , 23 ]. Thus, the objective of the present study was to determine if maternal consumption of HSP + NAR during pregnancy and lactation compromises BMD, bone structure, and biomechanical strength in male CD-1 offspring throughout development and into early adulthood.…”

Maternal vitamin D deficiency increases the risk of obesity in male mice offspring by affecting the immune response

“…The reasons for the observed harmful effects of insufficient maternal VD intake on the weight gain include an unhealthy trabecular bone structure (31), unreasonable colonization of intestinal flora (30), greater susceptibility to HFD-induced adipocyte hypertrophy among others (35). Adipocyte hypertrophy could lead to the alterations in immune cell populations after the onset of obesity.…”

“…In an epidemiological research, low VD status was found in about 69% of the pregnant women in China (27). Despite the known effects of maternal VD deficiency on the obesity of the offspring, clinical and animal studies designed to evaluate the effect on body fat mass in the offspring have produced mixed results owing to several methodological limitations (28–31). Moreover, only a few studies have reported on the possible mechanisms underlying the effects of maternal VD deficiency on the body weight of the offspring expect for its effects on adipocyte proliferation (30).…”