Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation

Abstract

With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.

Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue

“…Whole-body dysfunction in glucose metabolism comes later in life in other models of fetal programming. For example, glucose tolerance testing has been done in fetal programming models that are older than the mice used in this study [55,74,75]. Low protein models of fetal programming have observed that young offspring who are predisposed to diabetes with aging have reduced insulin secretion but only slight or no changes were observed in glucose intolerance [75,76].…”

Interleukin 1 Receptor 1 Knockout and Maternal High Fat Diet Exposure Induces Sex-Specific Effects on Adipose Tissue Adipogenic and Inflammatory Gene Expression in Adult Mouse Offspring

“…It is now well-accepted that maternal dietary stressors during pregnancy can have a marked impact on the risk of obesity and cardiometabolic disease in offspring during later life (Reynolds et al, 2017;Chang et al, 2019). Furthermore, the critical windows where early life nutrition and environment influence later metabolic health coincide with the development of the immune system.…”

Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

“…Several studies have linked developmental exposure to high levels of saturated fat through the maternal diet with altered glucocorticoid signalling and HPA axis programming in adult offspring. In particular, high levels of saturated fats in maternal diet induce pro-inflammation in the mother that reaches the developing offspring during gestation and early postnatal life through milk transfer [16][17][18][19]. In humans, maternal high-fat diet (HFD) is linked to metabolic disorders and anxiety in children [20][21][22][23][24][25][26].…”