Specialized Topics  
 Appetite Control    
 Appetite Hormones
 Weight Loss Genes
 Eating & Sex         
 Ghrelin & Leptin     
 Dr K's Diet            

How Do We Control Our Appetites?

If pleasure drives humans better than pain, why do so many people create pain in their lives by becoming overweight?  The answer for anyone who is too heavy is that the pleasure outranks the pain.

Eating for pleasure is a big part of the obesity problem. The ability to reverse obesity comes from our brain. There the hypothalamus acts as the primary coordinator of signals that regulate energy balance and memory.

A new anti-obesity drug to help obese people turn off these pleasurable or  “hedonic” aspects of food is in experimental trials. When energy pathways lead to weight gain, these pills can reverse that effect, resulting in weight loss.

Its action depends in large part on the endocannabinoid system or ECS, which is a human signaling system that plays a role in the regulation of energy balance and fat and sugar metabolism. Intense stimulation of the system, regulated by these cannabinoid receptors, makes us feel hungry even if we just ate.

The cannabinoid system has receptors called endocannabinoids. They play a major role in the regulation of food intake and feeding behavior. The cannabinoid system, active in your hypothalamus, contributes to your energy balance, under the control of the hormone leptin. You may recall that leptin produces that feeling of fullness that makes you stop eating.

Two specific endocannabinoid receptors have been identified, CB1 and CB2. These receptors are in high concentrations in the brain, liver, muscle, gut, and fat tissue. They are also present in the salivary glands where they both decrease salivary production and increase hunger.  

Generally, these receptors appear to be found in areas of our body responsible for altering energy balance, feeding behavior, liver fat production, and glucose balance, or in other words they are everywhere.

Another component of cannabinoid-mediated food intake appears to involve both reward pathways and the pleasurable aspects of eating. Since the cannabinoid system contributes to both pathways, it offers an attractive treatment for obesity and other eating disorders.  

Increased activity of the ECS is strongly associated with both oveweight and high cholesterol. Overactivity of the ECS decreases the cytokine, adiponectin. This protein lowers insulin and helps us lose weight. 

Certain stimuli that encourage food-seeking behavior prove that endocannabinoids can control our brain’s reward processes.  Neurologists know that smoking or eating cannabis can turn on specific receptors in our brain. This is why marijuana causes the “munchies” and eating habits fly out of control. Tetrahydrocannabinol or THC stimulation of these endocannabinoid receptors produces both weight gain and euphoria.

What if you could turn off these “hedonic” aspects of food? What if there was a drug to help you resist the cravings? When you want chocolate what if you could substitute making love or laughing at a good comedy?

In ongoing clinical trials, treatment with the endocannabinoid inhibitor, called Acomplia® or Zimulti®, developed by the scientists at Sanofi-Aventis, did exactly that. Acomplia, the Canadian brand of rimonobant, not only reduced excess body weight, but also lowered blood pressure in patients with high blood pressure. In obese humans, rimonobant improved all of the following: insulin sensitivity, corrected dyslipidemia, plus it decreased the incidence of metabolic syndrome. , , , , .

Rimonobant is being perfected in Europe. It can make your brain think you are full, even if your stomach is empty.  It sounds pretty good. It was released in Canada in 2006. The FDA was planning to release it in USA in 2007 but it has been postponed pending further testing to sometime in 2010.

The Rimonobant in Obesity-Lipids study confirmed that rimonobant significantly reduced body weight and waist circumference, while improving several metabolic risk factors in high-risk patients who are overweight or obese.

The beneficial effects of 20 mg of rimonobant were maintained after two years of treatment. Rimonobant also helped people quit smoking without the associated weight-gain. From August 2001 to April, 2004 clinical trials in over 3000 patients across 72 centers in Canada and the US, found a high dropout rate due to nausea and depression with rimonobant.  However, the beneficial effects on the cardiovascular disease were very positive.

Although a significant number of patients reduced their waist size in addition to losing weight while taking rimonobant , the FDA felt that the side effects were still too risky as after a year only 5 percent of weight loss was maintained.   This is the same success rate as most diet pills.

By blocking the pleasurable aspect of eating, for the first time in diet history, rimonobant offered a potential treatment for human obesity and other eating disorders. These are so common that the FDA must be certain of the safety of such a blockbuster drug.

Rimonobant is only the first of a new class of anti-obesity drugs coming down the pike. By blocking the pleasurable aspect of eating, rimonobant presents a novel treatment for human obesity and other eating disorders.

You may not be able to buy rimonobant in any state, but at your local drugstore, another effective diet aid is sold over the counter as Ali®.  The medication, metformin, is available on prescription as Glucophage®. These two have been used safely in combination to fight obesity.

Right now Meridia® is the only diet pill that the FDA approves for obesity treatment, but results in only a five percent loss over a year. Believe it or not, pedometers really work for tracking exercise. Drinking water before every meal and before desert helps decrease hunger as does popping a fish oil capsule with every meal. These are all techniques everyone can use.

When fat cells become engorged they release other factors that in turn affect insulin resistance. Eventually ongoing increase of inflammatory-promoting cytokines causes an inflammatory response leading to heart damage, high blood pressure and arthritis. In other words, being fat can damage both your heart and your joints.

As I mentioned, the stimulation of the CB1 receptor with pot or marijuana enhances food consumption and eating pleasure. Blocking the fat buildup from the different factors, promises a novel therapeutic approach to eating disorders and possibly an effective tool for reducing weight.

Rimonobant is the first of a new class of drugs that act by binding to the CB1 receptor and blocking hunger. In the long run, this blockade creates a decrease in ghrelin, the hunger hormone by increasing leptin, the satiety hormone.   The outcome is feeling less hungry and more satiated.

Controlling appetite allows heavy people to feel satisfied while their hunger is reduced, a perfect twosome. In clinical trials this anti-cannabinoid, rimonobant, has improved insulin sensitivity, corrected abnormal fat levels and also decreased the incidence of metabolic syndrome.

Another novel diabetes drug called Symlin® https://www.symlin.com/ has been developed by Amylin Pharmaceuticals. SYMLIN is a synthetic version of human amylin. Amylin is made in and secreted from the same cells in the pancreas that make and secrete insulin. These pancreatic cells are called beta cells.

Amylin and insulin work together with another hormone, glucagon, to maintain normal blood sugar concentrations. Insulin and amylin concentrations normally increase while glucagon levels decrease after meals. Amylin helps suppress glucagon secretion, thereby decreasing hunger. For more on amylin go to: http://www.amylin.com/pipeline/symlin.cfm.

Endocannabinoids and their receptors are expressed throughout the brain affecting circuits for food uptake. Appetite control is often difficult or impossible for many obese people, since they have developed an abnormal insensitivity to leptin or an increased sensitivity to ghrelin. That is they are either too hungry or never full enough to stop eating, even after a satisfying high protein meal.

Furthermore, cannabinoid blockage not only allows weight reduction by eliminating cravings, but also creates substantial reduction in waist size.  Loss of inches around the waist is associated with an improvement in HDL, insulin sensitivity and a decrease in heart disease risk. Your tape measure is your best guide to your body’s fat content. Use it regularly.

At this point, most of my readers may have reached an understanding of the complex connection between appetite control and obesity. In normal people, variations in blood sugar or glucose usually create hunger. Many different biological chemicals, mostly from the fat cell themselves, play a role in the fine-tuning of sugar metabolism. Understanding these interactions will help you to control your appetite.

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Significant improvements in the lipid profile, with an increase in high-density lipoprotein (HDL) cholesterol and a decrease in triglyceride levels were observed. Marked improvements in glucose tolerance and insulin levels resulted. Furthermore, the number of patients diagnosed with the metabolic syndrome was significantly reduced among rimonobant users. These medications also positively affect leptin, adiponectin and resistin.

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Copyright © 2006-2009, Abraham H Kryger, MD, DMD.

Contact the Doctor: DrK@wellnessmd.com

Disclaimer: This book is for people in whom being overweight contributes to poor health and interferes with a desired, active lifestyle.  It is recommended that you consult your own physician before using any of the medications or supplements discussed in this book. The plans are not for everyone, Wellness MD on the Web does not warranty the results and shall have no liability for information provided on this or any other Internet website. The recommendations for dietary supplements are only for health purposes.  This information is provided solely as a guideline to be used when discussing a weight loss program with a medical professional.