The prevalence of obesity has increased worldwide in the past ~50 years, reaching pandemic levels. Obesity represents a major health challenge because it substantially increases the risk of diseases such as type 2 diabetes mellitus, fatty liver disease, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnoea and several cancers, thereby contributing to a decline in both quality of life and life expectancy. Obesity is also associated with unemployment, social disadvantages and reduced socio-economic productivity, thus increasingly creating an economic burden. Thus far, obesity prevention and treatment strategies - both at the individual and population level - have not been successful in the long term. Lifestyle and behavioural interventions aimed at reducing calorie intake and increasing energy expenditure have limited effectiveness because complex and persistent hormonal, metabolic and neurochemical adaptations defend against weight loss and promote weight regain. Reducing the obesity burden requires approaches that combine individual interventions with changes in the environment and society. Therefore, a better understanding of the remarkable regional differences in obesity prevalence and trends might help to identify societal causes of obesity and provide guidance on which are the most promising intervention strategies.

Obesity: global epidemiology and pathogenesis.

‡We describe the use of singular value decomposition in transforming genome-wide expression data from genes 3 arrays space to reduced diagonalized ‘‘eigengenes’’ 3 ‘‘eigenarrays’’ space, where the eigengenes (or eigenarrays) are unique orthonormal superpositions of the genes (or arrays). Normalizing the data by filtering out the eigengenes (and eigenarrays) that are inferred to represent noise or experimental artifacts enables meaningful comparison of the expression of different genes across different arrays in different experiments. Sorting the data according to the eigengenes and eigenarrays gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype, respectively. After normalization and sorting, the significant eigengenes and eigenarrays can be associated with observed genome-wide effects of regulators, or with measured samples, in which these regulators are overactive or underactive, respectively.

Singular Value Decomposition for Genome-Wide Expression Data Processing and Modeling

https://foodaddictionsummit.org/documents/StressEatingandtheRewardSystem.pdf

Stress, eating and the reward system

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.

/pdf/dopamine-d2-receptors-in-addiction-like-reward-dysfunction-2yy8ytzlyq.pdf

Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats

Drugs of abuse have very different acute mechanisms of action but converge on the brain's reward pathways by producing a series of common functional effects after both acute and chronic administration. Some similar actions occur for natural rewards as well. Researchers are making progress in understanding the molecular and cellular basis of these common effects. A major goal for future research is to determine whether such common underpinnings of addiction can be exploited for the development of more effective treatments for a wide range of addictive disorders.

/pdf/is-there-a-common-molecular-pathway-for-addiction-32ztqi07ia.pdf

Is there a common molecular pathway for addiction

http://www.diabetichealthclinic.org/wp-content/uploads/2014/04/nihms36189.pdf

Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake

COLANTUONI, CARLO, PEDRO RADA, JOSEPH Mc-CARTHY, CAROLINE PATTEN, NICOLE M. AVENA,ANDREW CHADEAYNE, AND BARTLEY G. HOEBEL.Evidence that intermittent, excessive sugar intake causesendogenous opiod dependence. Obes Res. 2002;10:478–488.Objective: The goal was to determine whether withdrawalfrom sugar can cause signs of opioid dependence. Becausepalatable food stimulates neural systems that are implicatedin drug addiction, it was hypothesized that intermittent,excessive sugar intake might create dependency, as indi-cated by withdrawal signs.Research Methods and Procedures: Male rats were food-deprived for 12 hours daily, including 4 hours in the earlydark, and then offered highly palatable 25% glucose inaddition to chow for the next 12 hours. Withdrawal wasinduced by naloxone or food deprivation. Withdrawal signswere measured by observation, ultrasonic recordings, ele-vated plus maze tests, and in vivo microdialysis.Results: Naloxone (20 mg/kg intraperitoneally) causedsomatic signs, such as teeth chattering, forepaw tremor,and head shakes. Food deprivation for 24 hours causedspontaneous withdrawal signs, such as teeth chattering.Naloxone (3 mg/kg subcutaneously) caused reduced timeon the exposed arm of an elevated plus maze, whereagain significant teeth chattering was recorded. The plusmaze anxiety effect was replicated with four controlgroups for comparison. Accumbens microdialysis re-vealed that naloxone (10 and 20 mg/kg intraperitoneally)decreased extracellular dopamine (DA), while dose-depen-dently increasing acetylcholine (ACh). The naloxone-inducedDA/ACh imbalance was replicated with 10% sucrose and 3mg/kg naloxone subcutaneously.Discussion: Repeated, excessive intake of sugar created astate in which an opioid antagonist caused behavioral andneurochemical signs of opioid withdrawal. The indices ofanxiety and DA/ACh imbalance were qualitatively similarto withdrawal from morphine or nicotine, suggesting thatthe rats had become sugar-dependent.Key words: glucose, addiction, dopamine, plus maze,acetylcholine

/pdf/evidence-that-intermittent-excessive-sugar-intake-causes-n6chypfz65.pdf

Evidence That Intermittent, Excessive Sugar Intake Causes Endogenous Opioid Dependence

Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell.

Objectives 
We propose that highly processed foods share pharmacokinetic properties (e.g. concentrated dose, rapid rate of absorption) with drugs of abuse, due to the addition of fat and/or refined carbohydrates and the rapid rate the refined carbohydrates are absorbed into the system, indicated by glycemic load (GL). The current study provides preliminary evidence for the foods and food attributes implicated in addictive-like eating.


Design 
Cross-sectional.


Setting 
University (Study One) and community (Study Two).


Participants 
120 undergraduates participated in Study One and 384 participants recruited through Amazon MTurk participated in Study Two.


Measurements 
In Study One, participants (n = 120) completed the Yale Food Addiction Scale (YFAS) followed by a forced-choice task to indicate which foods, out of 35 foods varying in nutritional composition, were most associated with addictive-like eating behaviors. Using the same 35 foods, Study Two utilized hierarchical linear modeling to investigate which food attributes (e.g., fat grams) were related to addictive-like eating behavior (at level one) and explored the influence of individual differences for this association (at level two).


Results 
In Study One, processed foods, higher in fat and GL, were most frequently associated with addictive-like eating behaviors. In Study Two, processing was a large, positive predictor for whether a food was associated with problematic, addictive-like eating behaviors. BMI and YFAS symptom count were small-to-moderate, positive predictors for this association. In a separate model, fat and GL were large, positive predictors of problematic food ratings. YFAS symptom count was a small, positive predictor of the relationship between GL and food ratings.


Conclusion 
The current study provides preliminary evidence that not all foods are equally implicated in addictive-like eating behavior, and highly processed foods, which may share characteristics with drugs of abuse (e.g. high dose, rapid rate of absorption) appear to be particularly associated with “food addiction.”

/pdf/which-foods-may-be-addictive-the-roles-of-processing-fat-3psuklug0h.pdf

Nicole M. Avena

Papers

Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake

Evidence That Intermittent, Excessive Sugar Intake Causes Endogenous Opioid Dependence

Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell.

Which Foods May Be Addictive? The Roles of Processing, Fat Content, and Glycemic Load

Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity.