The Impact of Chronic Social Stress and Consumption of an Obesogenic Diet on the Trajectory of Insular Development in Infant and Juvenile Female Macaques Open Access

Abstract

Childhood obesity is a public health problem that continues to rise in the United States. Due to the long-term negative consequences in mental health, it is crucial to learn how children that are exposed to obesogenic, highly caloric diets (HCD) are impacted neurodevelopmentally. The consumption of obesogenic diets and the presence of chronic social stress are often comorbid, especially for children with a low socioeconomic status (SES). Both cause overlapping, potentially synergizing negative health effects. This longitudinal study investigates the effects of postnatal exposure to obesogenic diets and chronic psychosocial stress (social subordination stress) using a translational macaque model. The study followed 41 female macaques at Yerkes National Primate Research Center (YNPRC). There were 21 dominant animals from the top third of the hierarchy, and 20 subordinate animals from the bottom third of the hierarchy. Monkeys had access to either only low-calorie diet (LCD), or to both high-calorie diet (HCD) and LCD (Choice diet) from birth. Food intake (kilocalories (Kcal)) was recorded using radio-frequency identification (RFID) chips in subjects’ wrists that opened automatic feeders according to the diet assigned at birth. Cumulative Kcal consumption was measured from birth to 6 months and from 6 months to 16 months. Body weights were measured at birth, 2 weeks, 6 months, and 16 months.

Brain structural MRI (sMRI) scans were collected at 2 weeks, 6 months, and 16 months of age. This study focuses particularly on the developmental effects of postnatal stress and diet on the insula (and each of its subregions, including the agranular insula (AI), dysgranular insular (DI), and insular proisocortex (IPro)) due to its implications in emotional/limbic, socio-cognitive, and interoceptive functions. HCD exposure was associated with larger overall brain size (intracranial volume, or ICV) and insula and its subregions’ volumes throughout development. Some effects emerged at 2 weeks, suggesting that maternal factors might mediate these neurodevelopmental impacts. These findings suggest that postnatal exposure to obesogenic diets is associated with increased whole-brain and insular growth in primates. Interestingly, social rank did not have significant effects for ICV nor insular development in this study, which contrasts previous literature. 

Table of Contents

Table of Contents

Introduction ........................................................................................................................... 1

The Effects of Obesogenic Diets and Chronic Stress.......................................................................... 1

The Macaque Social Subordination Stress Model ............................................................................. 4

Functions of the insular cortex subregions and insular relations to stress and diet conditions.......... 8

Aim and Hypotheses ...................................................................................................................... 13

Methods............................................................................................................................... 15

Subjects, Housing and Experimental Design ................................................................................... 15

Diet Conditions .............................................................................................................................. 17

Structural Magnetic Resonance Imaging (sMRI) ............................................................................. 19

Acquisition of MRI Images................................................................................................................................. 19

sMRI Data Processing ........................................................................................................................................ 20

Statistical Analysis ......................................................................................................................... 22

Results ................................................................................................................................. 24

Structural MRI data (RM ANOVA) .................................................................................................. 24

Intracranial volumes (ICV) ................................................................................................................................. 24

Whole Insula Volumes....................................................................................................................................... 24

Agranular Insula (AI) Volumes ........................................................................................................................... 25

Dysgranular Insula (DI) Volumes ....................................................................................................................... 26

Granular Insula (GI) Volumes ............................................................................................................................ 27

Insular Proisocortex (IPro) Volumes .................................................................................................................. 27

Body Weight and Kilocalories consumed of the LCD and HCD Diets (LMM) .................................... 28

Discussion ............................................................................................................................ 29

Summary ....................................................................................................................................... 29

Kilocalorie Consumption and Body Weight .................................................................................... 30

Diet Effects .................................................................................................................................... 31

Brain Growth Mechanisms Relevant to Diet................................................................................... 35

Absence of Rank Effect .................................................................................................................. 36

Relevance of the Amygdala............................................................................................................ 36

Limitations and Future Studies....................................................................................................... 37

Significance.................................................................................................................................... 39

Tables and Figures................................................................................................................ 41

Table 1. Experimental Groups ........................................................................................................ 41

Table 2. Percent composition of nutrients in LCD and HCD pellets.................................................. 42

Figure 1. Experimental Design ........................................................................................................ 43

Figure 2. Atlases and Insular Subregions ........................................................................................ 44

Figure 3. Effects of social rank, diet, and age on intracranial volume (ICV) development ................ 45

Figure 4. Effects of social rank, diet, and age on whole insula volume development ...................... 46

Figure 5. Effects of social rank, diet, and age on agranular insula (AI) volume development........... 47

Figure 6. Effects of social rank, diet, and age on dysgranular insula (DI) volume development ....... 48

Figure 7. Effects of social rank, diet, and age on granular insula (GI) volume development ............ 49

Figure 8. Effects of social rank, diet, and age on insular proisocortex (IPro) volume development.. 50

Figure 9. Effects of social rank, diet, and age on body weight ......................................................... 51

Figure 10. Effects of social rank, diet, and age on kilocalorie consumption of each diet .................. 52

References............................................................................................................................ 53 

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Obesity Macaques Neuroscience Chronic Stress Insula Diet
Committee Chair / Thesis Advisor	Daniel Coppeto, Emory University Zsofia Kovacs-Balint, Emory University Jocelyne Bachevalier, Emory University Mar Sanchez, Emory University

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