Part 1 – Could Our Unhealthy Eating Cause Brain Changes, Neuroinflammation, and Obesity? Yes
In July of 2007, Duke’s Kelly Brownell and I hosted the first meeting of its kind at Yale University. This meeting became known as the Historic Yale Conference on Food and Addiction [1]. Interested in whether and how highly palatable, manufactured, and fast foods might affect the brains in ways similar to classic abuse substances were brought together for three days of presentations and discussions [2].
This Yale Conference’s 40 global experts on neuroscience, gastroenterology, obesity, diet, exercise, diabetes, psychiatry, bariatrics, and addiction came together for three days of discussions and debate about food and sugar addiction controversies medicine. Conferees were amazed that so much great science and work was going on, much of which they had not heard of before.
Since that time, the number of investigators working in this field has increased. Also, basic and translational science has developed and matured. Yale Historic Conference alumni continue to lead these studies with the ground-breaking work of Yale’s Dr. Dana Small [3], director of the Modern Diet and Physiology Research Center, Mt Sinai’s Dr. Nicole Avena [4], and Ashley Gearhardt’s group at Michigan [5] standing out.
Global Obesity
The prevalence of obesity in children and adolescents worldwide has quadrupled since 1975. The global prevalence of childhood overweight and obesity increased from 4.2% in 1990 to 6.7% in 2010. These trends are expected to continue, if not accelerate.
WHO reported recently that most of the world’s population live in countries where overweight and obesity kills more people than underweight [6]. Thirty-eight million children under the age of 5 were overweight or obese in 2019.
Over 340 million children and adolescents aged 5-19 were overweight or obese in 2016. The prevalence may reach 9.1% or approximately 60 million children in 2020. In developing countries, the combined prevalence was 6.1% in 2010 and may exceed 8.6% in 2020 [7].
Obesity early in life is a crucial predictor of obesity later in life. In 2016, more than 1.9 billion adults were overweight, and over 650 million were obese. While overeating and obesity is a common, global, preventable [8] disease, it is poorly understood.
Children and adolescents with obesity have more than a fivefold likelihood of becoming obese adults. Globesity or the global prevalence of obesity among youth has risen from 4% in 1975 to over 18% in a short period.
Obesity impacts the lives of children and adolescents in many ways. Overweight children report reduced self-esteem, mood, mental health, physical health, and adult obesity and mortality rates. Overall, obesity affects ∼35% of US children and adolescents.
Obesity has been defined using body mass index (BMI) ) or BMI scores adjusted for age and sex in children. But it is challenging to quantify the excessive amount of fat accumulation and relate these to current and future health consequences.
However, BMI as a predictive measure has been challenged, and more recently, experts have focused on waist circumference. Waist measurements may be a better estimate of visceral adiposity in children within a normal BMI range (e.g., <85% percentile). Highly processed foods produce craving and wanting an even reported withdrawal when removed from the diet [9].
How Does Obesity in Children Continue Through Adulthood
Previous work has consistently observed relationships between reward-related brain regions’ measures and the nucleus accumbens [NAcc]). Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain [10].
Recent animal and human studies suggest [11] a novel and quite a different model for food reward. These Yale studies reveal the existence of subcortical body-to-brain neural pathways linking gastrointestinal nutrient sensors to the brain’s reward regions.
Unexpectedly, consciously perceptible hedonic qualities appear to play a less relevant, and mostly transient, role in food reinforcement. In this new Small model, gut-brain reward pathways not only exist but serve as a bypass to cranial taste, aroma sensory receptors, and the cortical networks that comprise flavor perception.
They instead reinforce behaviors independently of the cognitive processes that try to control or influence our dietary decisions. Dopamine, NAcc, and reinforcement of hedonic but unhealthy eating behaviors and outcomes have been suggested since our earliest work. It is unclear what an unhealthy diet does to the brain and reinforcement areas to perpetuate poor eating choices.
We know that drugs of abuse cause dopamine release in the NAcc and that dopamine is released in anticipation of such reward. Over time, dopamine overstimulation causes downregulation and a dopamine or pleasure deficiency syndrome.
A greater density of cells in the Nucleus Accumbens, as described by our group and others as a critical natural and drug of the brain’s abuse reward center, has been a focus of studies of sugar self-administration and overeating as well as obesity. A new Yale University study shows that the density of pleasure-related cells found in children’s brains must be related to overeating and body mass as an adult.
This new Yale study published Oct. 12 in the Proceedings of the National Academy of Sciences [12] supports the general idea of manufacturing, fast, or hedonic foods are acting as rewarding substances of abuse. This study extends earlier hypotheses and analyses and is the first to suggest that a greater concentration of specialized cells in the nucleus accumbens is a marker for eventual obesity.
A diet high in sugar or calories or other unhealthy eating might trigger an inflammatory response. This inflammatory response can start a vicious cycle with overeating causing more overeating yet [13]. Yale lead researcher, Dr.Casey, noted that rates of childhood obesity worldwide have quadrupled over the past 40 years. That, she said, is in part due to greater accessibility to and consumption of unhealthy foods [14].
“Inflammation is known to be associated with obesity, but exactly how it is operating in the human brain has been challenging to investigate,” said Richard Watts, director of the Yale Brain Imaging Center. Using a novel MRI technique called Restriction Spectrum Imaging, which allows for a closer look at microstructures within the brain, the team investigated the cell density of the nucleus accumbens and its involvement in drug reinforcement, reward, motivation, and eating behavior.
They analyzed the National Institutes of Health-funded Adolescent Brain Cognitive Development (ABCD) study data of brain development and health in over 10,000 children. The main and very surprising finding was that the Yale researchers reported that the higher the density of cells in the nucleus accumbens, the larger the child’s waist circumference.
“An even more impressive finding was that the density of cells in this region predicted increases in waist circumference and body mass index one year later,” said Kristina Rapuano, a psychology postdoctoral fellow at Yale and first author on the study [15].
Triglycerides can be metabolized within the brain’s reward system and modulate DA-associated brain responses to food cues, especially in individuals with reward deficiency or reduced dopamine. Just eating energy-dense or high-fat foods may induce changes in the brain’s DA signaling that cause reward deficit and compulsive overeating behaviors [16].
Previous studies in animals have shown that a diet high in saturated fats spurs neuroinflammation in the brain, which increases the number of cells in the nucleus accumbens. This accumulation of cells can trigger compulsive eating in animals.
“It’s a vicious cycle. Eating bad food leads to wanting more bad food. These data provide a possible brain mechanism for this idea,” said BJ Casey, professor of psychology at Yale and co-author of the study. “This study is a step towards better understanding the neurobiological mechanisms underlying childhood weight gain, which will be critically important to inform early intervention and obesity prevention strategies,” Casey said [17].
The current study observed significant associations between obesity and brain microstructure measures in a large cohort of 9- and 10-y-old children, particularly within the NAcc.Person-to-person differences in waist circumference were directly related to tissue cellularity in several subcortical regions—including the NAcc, caudate, putamen, and pallidum. Among all the brain regions analyzed, NAcc cellularity and density were most strongly related to waist circumference increases at one year follow up.
NAcc cellularity might be a neuropathological marker reflecting microstructural changes in the brain’s reward-related regions, directly caused by an overconsumption of unhealthy foods. A substantial body of work has documented the role of dopaminergic pathways in motivating eating behavior, which may provide insight into the link between weight change and cellular-level differences in the NAcc.
For example, previous studies have demonstrated decreased striatal dopamine availability in obese adults (40), suggested to occur due to frequent overeating and chronic stimulation. Similar to reward deficiency models of addiction [18], a down-regulation of dopamine may lead individuals to overeat in an attempt to compensate for this deficit.
My colleagues at Princeton, Hoebel, and Avena, clearly showed that decreased mesolimbic dopaminergic activity is associated with increased consumption of high-fat foods in rodents. Avena and also Gearhardt have reported similar data on sugar, fat, and hedonic foods and addiction in humans.
Treatment Implications of Overeating and Obesity links to Substance Use Disorders
A family history of substance use is a well-established risk factor for greater substance use in adolescence and adulthood. The biological vulnerability hypothesis proposes that a family history of substance use might also confer risk for obesogenic eating behavior because of similar rewarding characteristics between substances and processed foods high in refined carbohydrates and fat.
A family history of substance use is linked with sweet liking and obesity in adults. A family history of substance use may be a crucial transdiagnostic risk factor that identifies children at risk for obesogenic, reward-driven eating behaviors [19].
The incentive-sensitization theory of addiction is relevant to food and eating. Motivational salience, or “wanting,” increases disproportionately with food “liking,” or the hedonic pleasure associated with consumption. We have considered food “liking” related to opioid and endocannabinoid brain pathways.
The more primitive food “wanting” appears related to dopamine and the mesolimbic dopamine system, which we have studied for over four decades. So, it seems that dopamine activity motivates eating behavior but can also be shut down by overconsumption.
Twenty years ago, addiction was defined by tolerance and withdrawal rather than the current emphasis on attachment and acquired drive for the drug. The definition of addiction changed shortly after our group and other cocaine researchers showed that cocaine was addicting but without an abstinence syndrome.
Addiction was more like an awful relationship or some fatal attraction. The definition of addiction has been changed so much in the DSM 5 that the word addiction itself was replaced with “use disorders.” Addiction now includes compulsive behaviors like gambling, and internationally, gaming. Pathological gambling was widely considered a bad habit at one time, but now is in DSM 5 and is considered a prime example of behavioral addiction. What will occur with food?
Please See – Overeating and Obesity 2021 Update on What We Know and What Medicine-Surgery Can Do – Part 2
Resources:
1. https://news.yale.edu/2007/07/09/yale-hosts-historic-conference-food-and-addiction
2. https://news.yale.edu/2007/07/09/yale-hosts-historic-conference-food-and-addiction
3. https://medicine.yale.edu/profile/dana_small/
4. https://labs.icahn.mssm.edu/avenalab/
5. https://lsa.umich.edu/psych/people/faculty/agearhar.html
6. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
7. Wang, Y., & Lim, H. (2012). The global childhood obesity epidemic and the association between socio-economic status and childhood obesity. International review of psychiatry (Abingdon, England), 24(3), 176–188. https://doi.org/10.3109/09540261.2012.688195
8. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
9. Schulte EM, Smeal JK, Lewis J, Gearhardt AN. Development of the Highly Processed Food Withdrawal Scale. Appetite. 2018 Dec 1;131:148-154. doi: 10.1016/j.appet.2018.09.013. Epub 2018 Sep 15. PMID: 30227182.
10. Berland C, Montalban E, Perrin E, Di Miceli M, Nakamura Y, Martinat M, Sullivan M, Davis XS, Shenasa MA, Martin C, Tolu S, Marti F, Caille S, Castel J, Perez S, Salinas CG, Morel C, Hecksher-Sørensen J, Cador M, Fioramonti X, Tschöp MH, Layé S, Venance L, Faure P, Hnasko TS, Small DM, Gangarossa G, Luquet SH. Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons. Cell Metab. 2020 Apr 7;31(4):773-790.e11. doi: 10.1016/j.cmet.2020.02.010. Epub 2020 Mar 5. PMID: 32142669; PMCID: PMC7250662.
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11. de Araujo IE, Schatzker M, Small DM. Rethinking Food Reward. Annu Rev Psychol. 2020 Jan 4;71:139-164. doi: 10.1146/annurev-psych-122216-011643. Epub 2019 Sep 27. PMID: 31561741.
12. Rapuano KM, Laurent JS, Hagler DJ Jr, Hatton SN, Thompson WK, Jernigan TL, Dale AM, Casey BJ, Watts R. Nucleus accumbens cytoarchitecture predicts weight gain in children. Proc Natl Acad Sci U S A. 2020 Oct 12:202007918. doi: 10.1073/pnas.2007918117. Epub ahead of print. PMID: 33046629.
13. https://news.yale.edu/2020/10/12/brain-imaging-can-predict-childhood-weight-gain
14. https://news.yale.edu/2020/10/12/brain-imaging-can-predict-childhood-weight-gain
15. https://news.yale.edu/2020/10/12/brain-imaging-can-predict-childhood-weight-gain
16. Berland C, Montalban E, Perrin E, Di Miceli M, Nakamura Y, Martinat M, Sullivan M, Davis XS, Shenasa MA, Martin C, Tolu S, Marti F, Caille S, Castel J, Perez S, Salinas CG, Morel C, Hecksher-Sørensen J, Cador M, Fioramonti X, Tschöp MH, Layé S, Venance L, Faure P, Hnasko TS, Small DM, Gangarossa G, Luquet SH. Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons. Cell Metab. 2020 Apr 7;31(4):773-790.e11. doi: 10.1016/j.cmet.2020.02.010. Epub 2020 Mar 5. PMID: 32142669; PMCID: PMC7250662.
17. https://news.yale.edu/2020/10/12/brain-imaging-can-predict-childhood-weight-gain
18. Blum K, Thanos PK, Oscar-Berman M, Febo M, Baron D, et al. 2015. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction. J Reward Defic Syndr 1(3): 95-104.
19. Cummings JR, Lumeng JC, Miller AL, Hyde LW, Siada R, Gearhardt AN. Parental substance use and child reward-driven eating behaviors. Appetite. 2020 Jan 1;144:104486. doi: 10.1016/j.appet.2019.104486. Epub 2019 Oct 9. PMID: 31605723; PMCID: PMC6890229.
About the Author:
Mark S. Gold, M.D., Professor, Washington University School of Medicine – Department of Psychiatry, served as Professor, the Donald Dizney Eminent Scholar, Distinguished Professor and Chair of Psychiatry from 1990-2014. He was the first Faculty from the College of Medicine to be selected as a University-wide Distinguished Alumni Professor and served as the 17th University of Florida’s Distinguished Alumni Professor.
Dr. Gold is also a Distinguished Fellow, American Society of Addiction Medicine; Distinguished Life Fellow, the American Psychiatric Association; Distinguished Fellow, American College of Clinical Pharmacology; Clinical Professor of Psychiatry, Tulane University School of Medicine; Professor( Adjunct), Washington University in St Louis, School of Medicine, Department of Psychiatry; National Council, Washington University in St Louis, Institute for Public Health
Learn more about Mark S. Gold, MD
The opinions and views of our guest contributors are shared to provide a broad perspective of addictions. These are not necessarily the views of Weight Hope, but an effort to offer a discussion of various issues by different concerned individuals.
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Published on November 2, 2020. Published on WeightHope.com
Reviewed by Jacquelyn Ekern, MS, LPC on November 2, 2020