Maternal Obesity Programming of Perivascular Adipose Tissue and Associated Immune Cells: An Understudied Area With Few Answers and Many Questions

Abstract

At present, the worldwide prevalence of obesity has become alarmingly high with estimates foreshadowing a continued escalation in the future. Furthermore, there is growing evidence attributing an individual’s predisposition for developing obesity to maternal health during gestation. Currently, 60% of pregnancies in the US are to either overweight or obese mothers which in turn contributes to the persistent rise in obesity rates. While obesity itself is problematic, it conveys an increased risk for several diseases such as diabetes, inflammatory disorders, cancer and cardiovascular disease (CVD). Additionally, as we are learning more about the mechanisms underlying CVD, much attention has been brought to the role of perivascular adipose tissue (PVAT) in maintaining cardiovascular health. PVAT regulates vascular tone and for a significant number of individuals, obesity elicits PVAT disruption and dysregulation of vascular function. Obesity elicits changes in adipocyte and leukocyte populations within PVAT leading to an inflammatory state which promotes vasoconstriction thereby aiding the onset/progression of CVD. Our current understanding of obesity, PVAT and CVD has only been examined at the individual level without consideration for a maternal programming effect. It is unknown if maternal obesity affects the propensity for PVAT remodeling in the offspring, thereby enhancing the obesity/CVD link, and what role PVAT leukocytes play in this process. This perspective will focus on the maternal contribution of the interplay between obesity, PVAT disruption and CVD and will highlight the leukocyte/PVAT interaction as a novel target to stem the tide of the current obesity epidemic and its secondary health consequences.

Maternal Obesity and Kawasaki Disease-like Vasculitis: A New Perspective on Cardiovascular Injury and Inflammatory Response in Offspring Male Mice

“…Moreover, maternal obesity induces metabolic dysfunction in offspring, and the mechanisms involved decreased expression of genes that were related to adipocyte proliferation and differentiation, and insulin signaling and lipid mobilization [31,32]. Additionally, maternal obesity may program perivascular adipose tissue and associated immune cells in offspring, thereby enhancing the obesity/cardiovascular disease link [33,34].…”

Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy

“…The proximity of PVAT to blood vessels underscores its role in tonal regulation via its secretory modulators [106][107][108]. The capacity to secrete such diverse arrays of biologically active molecules is due to the heterogeneous composition of PVAT which includes not only adipocytes, but leucocytes, neurons, and multipotent progenitor cells [108][109][110]. There are many types of immune cells in PVAT, such as CD4 + and CD8 + T cells, B cells, natural killer (NK) cells, macrophages, mast cells, and neutrophils [106,108,110].…”

“…The capacity to secrete such diverse arrays of biologically active molecules is due to the heterogeneous composition of PVAT which includes not only adipocytes, but leucocytes, neurons, and multipotent progenitor cells [108][109][110]. There are many types of immune cells in PVAT, such as CD4 + and CD8 + T cells, B cells, natural killer (NK) cells, macrophages, mast cells, and neutrophils [106,108,110]. Indeed, PVAT depots have greater numbers and types of immune cells compared with other types of adipose tissue [111].…”

Maternal obesity and the impact of associated early-life inflammation on long-term health of offspring

“…The unbalanced response of monocytes to M1 and M2 stimulation in children of mothers with obesity might have detrimental effects on the inflammatory changes that could explain some of the chronic conditions associated with fetal reprogramming caused by exposure to maternal obesity (Cifuentes-Zuniga et al, 2017). Again, the majority of these studies are performed using circulating immune cells and likely do not represent the landscape of immune cells in different organ systems as informed by animal studies [e.g immune cells within adipose tissue (Corken and Thakali, 2021) and liver (Nash et al, 2021)]. Nevertheless, these findings raise the possibility that the long-term function of HSPC is altered in offspring born to mothers with obesity.…”