The Role of Bariatric Surgery on Brain and RewardPeter K Thanos, Ph. D.Stony Brook University

65% of the world's population is overweight and obesity kills more people than malnutrition.

Globally, 44% of diabetes, 23% of heart disease, 7–41% of certain cancers are attributable to being overweight and obesity (WHO, 2014).

A problem of major public health significance.

– Overeating and obesity are second only to tobacco in annual associated mortality; almost 400,000 deaths per year.

– Obesity is common, serious and costly

Over 20 years ago, Mark Gold first reported on the similarities of overeating and obesity to classic addictions.

• Highly palatable and energy dense refined carbohydrates, sweeteners, fats and processed foods have become substances of abuse. While Binge Eating Disorder (BED) is in the DSM V, Overeating and Obesity is not. However, more and more people are considering the data on food as a “substance” in Substance Use Disorders (SUDs).

– Loss of control, use despite diabetes and other catastrophic consequences, changing priorities and loss of control would make criteria for SUD.

Neuroimaging studies have supported the hypothesis that loss of control over eating and obesity produces changes in the brain, which are similar to those produced by drugs of abuse.

Recently discovered messengers have effects in modulating eating behavior as well as have roles in alcohol and other drug dependencies.

-Treatment of obesity, from surgery to medications, often involves similar 12-step meetings. -Applying research methodologies applied to addictions may offer hope for understanding and development of common treatments.-Addiction: a chronic brain disease that involves both biological & environmental variables.

Gold, Frost & Jacobs, 2003

CDC, The National Health and Nutrition Examination Surveys (NHANES) 2012; Finkelstein et al. 2009

*41 million women and 37 million men aged 20 and over were obese in 2010. *Among children and adolescents aged 2–19, > 5 million girls and ~ 7 million boys were obese.

Annual medical cost of obesity in the U.S. was $147 billion in 2008; the medical costs for people who are obese were $1,429 higher than those of normal weight.

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Surgical intervention is an option for patients with clinically severe obesity (BMI [body mass index] ≥ 40 or ≥ 35 kg/m2 with comorbid conditions)when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity or mortality.

Bariatric surgery is safe & has been shown to be the most effective and long lasting treatment for morbid obesity and it results in significant weight loss.

200,000 adults / year in US have bariatric surgery. American Society for Metabolic & Bariatric Surgery. (2009).

The risk of death is about 0.1 percent[14] and the overall likelihood of major complications is about 4 percent.

Bariatric surgical outcomes: -Diabetes 1417 of 1846 (77%) resolved; 414 of 485 (85%) improved. RYGB: changes in gut hormone levels after RYGB, including increased anorectic hormones that induce satiety (e.g., GLP-1, PPY) and decreased levels of orexigens like ghrelin, an appetite-stimulating hormone.Sleep apnea: in severely obese prevalence 55- 100%. (Chan et al. 2004; Bouldin et al. 2006). RYGB decreased BMI by 17.5 and a 71% improvement in the apnea-hypopnia index (AHI). Greenburg et al. (2009). Dyslipidemia: Elevated triglycerides, LDL and low HDL. Associated with hypertension & metabolic Syndrome (MetS) (cluster of cardiovascular disease symptoms). 70% improvement following Bariatric Surgery at 2 year follow-up. (Buchwald et al. 2004).Hypertension: 62% resolved or improved (79%). (Buchwald et al. 2004).The projected risk for coronary heart disease following bariatric surgery decreased by 39% in men and 25% in women (Vogel et al. 2007).

• The Roux-en-Y Gastric Bypass (RYGB): considered the “gold standard” for bariatric surgery and is the most commonly performed operation. (Madura and DiBaise 2012)

• Involves creating a gastric pouch, Roux limb & biliary limb.

• After an RYGB, the size of the pouch restricts the volume of ingested food, and approximately 95% of the stomach, the entire duodenum and a portion of the jejunum are effectively bypassed.

Laparoscopic adjustable gastric band. Silicone ring around the upper part of the stomach, creating a small gastric pouch that restricts food intake.

Sleeve Sleeve Gastrectomy: Gastrectomy: Partial gastrectomy, Partial gastrectomy, in which the majority in which the majority of the greater of the greater curvature of the curvature of the stomach is removed stomach is removed and a tubular and a tubular stomach is createdstomach is created..

RYGB resulted in reduced preference and motivation for high concentrations of sugars and fats, with increased neural and behavioral responses to lower concentrations previously not registered as rewarding by obese subjects (Hajnal et al. 2010; Ochner et al. 2011;2012; Shin et al. 2011).

RYGB may bring about a beneficial effect on food choices either due to improved reward or avoidance of previously preferred highly stimulating foods, or both.

Increased risk among RYGB patients for use of alcohol (Ertelt et al. 2008; Hsu et al 1998; King et al 2012; Suzuki et al. 2012) or other substances (Conason et al.

2013; Dutta et al. 2006) raising concerns about development of alcohol use disorder (AUD) or addiction.

Due to these concerns, alcohol abuse represents a relative contraindication for most bariatric surgery programs.

We are interested in validating the clinical reports of increased alcohol use and determining the potential risk for alcohol abuse following RYGB in high-fat diet (HFD) obese rats.– Methods—Rats were given HFD or control diet (age of 4 weeks)

underwent RYGB (age 12 weeks) and had access along with their sham-operated obese controls and with lean rats to alcohol orally or intravenously.

We found that RYGB rats showed increased alcohol preference, and consumed twice as much alcohol as sham-operated obese controls and 50% more than normal-diet lean controls (Thanos et al. 2012).

Of special importance to separating gastrointestinal (GI) factors from more direct effects of alcohol on the brain, we found increased alcohol self-administration in RYGB rats to intravenous alcohol administration (Polston et al. 2013).

We concluded that RYGB increased alcohol consumption in obese RYGB rats both orally and intravenously. (Thanos et al 2012; Hajnal et al. 2012; Polston et al. 2013):

The lower alcohol intake in the obese controls than in the lean rats suggests that obesity may interfere with alcohol’s rewarding effects and RYGB may remove this protective effect. RYGB may facilitate alcohol consumption, which in vulnerable individuals could lead to abuse and addiction.

These findings suggest a biological cause and point to factors beyond known changes in GI absorption and pharmacodynamics of alcohol after RYGB (Hagedorn et al. 2007; Holt, 2001; Klochhoff et al. 2002).

Mechanisms: we propose that RYGB improves brain reward sensitivity. The neural mechanisms underlying how RYGB may increase alcohol use, and

whether this constitutes a risk for development of addiction remain poorly understood.

Current research is focused on investigating factors that may result in increased risk of AUD following RYGB and in particular the involvement of the ghrelin system as a potential underlying mechanism (Polston et al. 2013).