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Review
. 2022 Mar;23(3):e13392.
doi: 10.1111/obr.13392. Epub 2021 Nov 30.

Fetal programming of human energy homeostasis brain networks: Issues and considerations

Jerod M Rasmussen  1   2 , Paul M Thompson  3 , Sonja Entringer  1   2   4   5 , Claudia Buss  1   2   4   5 , Pathik D Wadhwa  1   2   5   6   7
Affiliations
Review

Fetal programming of human energy homeostasis brain networks: Issues and considerations

Jerod M Rasmussen et al. Obes Rev. 2022 Mar.

Abstract

In this paper, we present a transdisciplinary framework and testable hypotheses regarding the process of fetal programming of energy homeostasis brain circuitry. Our model proposes that key aspects of energy homeostasis brain circuitry already are functional by the time of birth (with substantial interindividual variation); that this phenotypic variation at birth is an important determinant of subsequent susceptibility for energy imbalance and childhood obesity risk; and that this brain circuitry exhibits developmental plasticity, in that it is influenced by conditions during intrauterine life, particularly maternal-placental-fetal endocrine, immune/inflammatory, and metabolic processes and their upstream determinants. We review evidence that supports the scientific premise for each element of this formulation, identify future research directions, particularly recent advances that may facilitate a better quantification of the ontogeny of energy homeostasis brain networks, highlight animal and in vitro-based approaches that may better address the determinants of interindividual variation in energy homeostasis brain networks, and discuss the implications of this formulation for the development of strategies targeted towards the primary prevention of childhood obesity.

Keywords: brain circuitry; childhood obesity; energy balance homeostasis; fetal programming.

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Conflict of interest statement

Declarations of interest: P.M.T. receives partial grant support from Biogen, Inc., for research unrelated to this manuscript. None of the other authors declares any conflict of interest.

Figures

Figure 1.
Figure 1.. Conceptual Model.
The conceptual model incorporates the role of fetal programming of the setpoint of energy homeostasis-related brain circuitry at birth into the process of fetal programming of offspring body composition.
Figure 2.
Figure 2.. Hormonal Inputs to the Central Regulation of Energy Homeostasis.
Hormonal orexegenic input to the CNS originates from stomach contraction, specific nutrient sensing in the gut, and peripheral energy substrate sensing. Anorexigenic signaling arises from stomach distension, nutrient sensing in the gut, and adipocytes. The CNS integrates these signals in order to regulate energy homeostasis through modulation of energy intake and expenditure.
Figure 3.
Figure 3.. Energy Homeostasis Relevant Brain Regions.
Highlighted brain regions are organized based on their network membership (color outline).
See this image and copyright information in PMC

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