Developmental programming of offspring adipose tissue biology and obesity risk

Abstract

Obesity is reaching epidemic proportions and imposes major negative health crises and an economic burden in both high and low income countries. The multifaceted nature of obesity represents a major health challenge, with obesity affecting a variety of different organs and increases the risk of many other noncommunicable diseases, such as type 2 diabetes, fatty liver disease, dementia, cardiovascular diseases, and even cancer. The defining organ of obesity is the adipose tissue, highlighting the need to more comprehensively understand the development and biology of this tissue to understand the pathogenesis of obesity. Adipose tissue is a miscellaneous and highly plastic endocrine organ. It comes in many different sizes and shades and is distributed throughout many different locations in the body. Though its development begins prenatally, quite uniquely, it has the capacity for unlimited growth throughout adulthood. Adipose tissue is also a highly sexually dimorphic tissue, patterning men and women in different ways, which means the risks associated with obesity are also sexually dimorphic. Recent studies show that environmental factors during prenatal and early stages of postnatal development have the capacity to programme the structure and function of adipose tissue, with implications for the development of obesity. This review summarizes the evidence for a role for early environmental factors, such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during gestation in the programming of adipose tissue and obesity in the offspring. We will also discuss the complexity of studying adipose tissue biology and the importance of appreciating nuances in adipose tissue, such as sexual dimorphism and divergent responses to metabolic and endocrine stimuli. Given the rising levels of obesity worldwide, understanding how environmental conditions in early life affects adipose tissue phenotype and the subsequent development of obesity is of absolute importance.

The Carbohydrate Threshold in Pregnancy and Gestational Diabetes: How Low Can We Go?

“…Models of maternal undernutrition have demonstrated that inadequate total maternal EI is tightly associated with reduced and stunted fetal growth patterns [ 43 ], but it is often not possible to separate the role of insufficient energy vs. carbohydrate intake. Moreover, both restricted and very high protein intake has been associated with low birth weight [ 44 , 45 , 46 ].…”

“…Importantly, in the cohorts from India and Malawi, higher carbohydrate intake was accompanied by modestly lower protein intake (11.5% and ~10%, respectively) [ 32 , 33 ]. This could be a potential factor in the SGA observations [ 44 ], although statistically protein intake was not associated with fetal growth. Collectively, the data suggest that a LC diet pattern may support appropriate fetal growth, but further studies are needed to separate the effects of LC from low EI.…”

“…Specific to pregnancy, there is concern that higher dietary fat intake could increase maternal TG and FFA, potentially increasing fetal exposure to maternal lipids secondary to heightened maternal insulin resistance, leading to overgrowth [ 57 ]. Fetal exposure to increased maternal lipids, particularly through high fat diets, has been linked with developmental programming of offspring obesity and fatty liver in animal models and in human cohorts [ 44 , 57 , 58 , 59 , 60 , 61 ].…”

“…No studies included women who consumed a very low carbohydrate diet ( Figure 1 ). Although in most of the studies protein intake was not related to fetal growth, higher and lower intakes are known to be related with growth restriction [ 44 ]; future studies are required to evaluate the effects of a LC diet with higher protein intake. Optimal protein and fat intake in pregnancy were not the focus of this review per se.…”

Loss of imprinting of the Igf2-H19 ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse

“…In light of accumulating evidence of sexual dimorphism in placental adaptations to genetic and/or environmental perturbations (Aykroyd et al, 2020; Barke et al, 2019; Kalisch-Smith et al, 2017; Napso et al, 2019; Rosenfeld, 2015) and offspring outcomes (Christoforou and Sferruzzi-Perri, 2020; Dearden et al, 2018; Rodgers and Sferruzzi-Perri, 2021), we accounted for fetal sex in our analyses. Whilst Jz size was increased in placentas of both male and female conceptuses in response to Jz-ΔICR1, the underlying mechanisms appear to exhibit a degree of sexual dimorphism.…”