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Life Extension Magazine

Life Extension Magazine June 2009
Reports

The Nine Pillars of Successful Weight Loss

By William Faloon
Pillar Number 7:Restore Healthy Adipocyte Signaling

Pillar Number 7: Restore Healthy Adipocyte Signaling

The adipocyte (fat cell) is the primary site for fat storage. Adipocytes of obese individuals are bloated with triglycerides, which is the form that most fat exists in the body. Fat storage and release is tightly regulated by adipocyte command signals.

Weight gain occurs when adipocytes (fat cells) enlarge with large amounts of triglycerides. Adipocytes accumulate excess triglycerides due to overeating, nutrient deficiencies, excessive stress, and other causes. These factors, however, fail to address the reason why aging individuals put on fat pounds despite eating less, taking dietary supplements, and following other practices that should in theory lead to weight loss.

Fat and Cancer

Excess body fat not only increases the risk of cardiovascular disease, it also increases the risk of deadly cancers. In one large European study, increasing body mass index was associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined.71 Recent studies have shown a powerful association between body fat content and kidney and liver cancers.72,73 By now, it should be no surprise to learn that weight loss, specifically body fat reduction, can lead to lowered risks for cancers just as it does for other devastating conditions.74,75 One study has estimated a reduction of 45% in the risk of breast cancer in women who lost more than about nine pounds.75

The aging process adversely affects the adipocyte command signal network, which helps explain the difficulty maturing individuals have in controlling their weight.

Adipocytes regulate their size and number by secreting command signals. The three command signals that regulate adipocytes are:

  • Leptin
  • Adiponectin
  • Glycerol-3-phosphate dehydrogenase.

A West African medicinal food called Irvingia gabonensis has been shown to favorably affect the three adipocyte command centers in the following ways:

LEPTIN

Released by adipocytes, leptin travels to the brain to perform two critical functions. First it signals the brain that enough food has been ingested and shuts down appetite. It then depletes bloated adipocytes by promoting the burning of stored triglycerides. Leptin is much more abundant in the blood of obese individuals, yet leptin functions to turn off appetite while promoting the burning of triglycerides that bloat our adipocytes. The reason why obese people have higher blood levels of leptin is that leptin receptor sites on cell membranes are inactivated by inflammatory factors in the body. Irvingia helps unblock “leptin resistance”.

ADIPONECTIN

The second command signal released by adipocytes is adiponectin. The transcription factors associated with adiponectin help determine the amount of triglycerides stored in adipocytes and number of adipocytes formed in the body. Higher levels of adiponectin enhance insulin sensitivity, which is a long established method to induce weight loss. Gene transcriptional factors involved with adiponectin are directly involved in sequential expression of adipocyte-specific proteins. Irvingia suppresses transcriptional factors involved in the formation of new adipocytes, while enhancing cell membrane insulin sensitivity by increasing adiponectin. High circulating levels of adiponectin have been shown to protect against coronary artery disease, whereas low adiponectin levels are observed in overweight individuals.

GLYCEROL-3-PHOSPHATE DEHYDROGENASE

Pillar Number 8:Inhibiting the Lipase Enzyme

An enzyme that facilitates the conversion of blood glucose into stored triglyceride fat is glycerol-3-phosphate dehydrogenase. The presence of this enzyme in the body reveals why low-fat diets alone fail to achieve sustained weight loss, i.e. the body will take ingested carbohydrates and convert them into stored triglyceride fat via the glycerol-3-phosphate dehydrogenase enzyme. Irvingia inhibits glycerol-3-phosphate dehydrogenase, thus reducing the amount of ingested sugars that are converted to body fat.

Clinical studies have demonstrated significant belly fat and total weight loss in response to taking a 150 mg Irvingia gabonensis extract twice daily. A mechanism for this weight loss reported by many Irvingia users is a reduction in appetite with a concomitant decrease in the number of ingested calories.

Pillar Number 8: Inhibiting the Lipase Enzyme

Orlistat is an inhibitor of pancreatic and gastric lipase. It decreases the intestinal absorption of ingested dietary triglycerides by 30%. By reducing the breakdown and absorption of dietary fat, orlistat enhances weight loss and lessens insulin resistance.

In studies of obese subjects, orlistat treatment improves insulin and glucose blood levels while significantly decreasing C-reactive protein, a marker for chronic inflammation. Orlistat treatment favorably influences other blood markers (such as leptin and adiponectin) that are involved with obesity.

In a one-year trial of overweight women, a group with metabolic syndrome treated with orlistat (120 mg three times a day) and lifestyle modification lost 20.5 pounds compared with only 0.44 pounds weight loss in the placebo control group. A group of overweight women without metabolic syndrome taking the same dose of orlistat + lifestyle modification lost 20.2 pounds more than the control group with metabolic syndrome.

Fat and Cardiovascular Disease

High body fat is of course strongly associated with cardiovascular disease—but the relationship is more complicated and subtle than we used to think. Atherosclerosis is clearly the result of the cycle of lipid oxidation, inflammation, and vascular injury, as mentioned above, but fat tissue causes other risks that are independent of plasma lipid levels. Acting as an endocrine organ, fat tissue can increase the flow of hormones (known as adipokines) involved in blood pressure control,26 potentially accounting directly for some of the hypertension we used to attribute simply to “stiff blood vessels” and “extra force needed to pump blood.”65 Again, it seems to be specifically the accumulations of abdominal fat that produce these remarkable and deadly effects.66 And again, it is fortunate that adequate reduction in body fat content through lifestyle changes, diet, and supplementation has been associated with decreased risk for cardiovascular catastrophes, such as heart attacks and strokes.67-70

Controlling Body Fat Content Safely

Despite the obvious dangers of obesity and specifically, elevated abdominal body fat content, most Americans have a hard time losing weight. Many turn to “quick-fix” solutions such as bariatric surgery (“stomach stapling”), which actually does provide some benefit in extreme cases,76 or to “diet pills” that are usually ineffective and often dangerous.77-81 The best and safest approaches to weight loss continue to be a modest reduction in caloric intake coupled with a careful increase in energy expenditure.

In a three-month open-label trial of overweight patients without type 2 diabetes treated with orlistat (120 mg three times a day), men lost 17.4 pounds and women lost 12.3 pounds. In overweight patients with type 2 diabetes mellitus, men lost 18.7 pounds and women lost 12.5 pounds. In this study, leptin levels decreased by 51% in men with type 2 diabetes and 25% in women with type 2 diabetes mellitus. Leptin levels dropped by 48% in overweight men and 23% in overweight women without type 2 diabetes mellitus. A reduction in leptin blood levels is considered a favorable response as it indicates a reduction in the “leptin resistance” phenomenon that so often precludes successful weight loss.

Pillar Number 9: Eat to Live a Long and Healthy Life

Not all studies demonstrate this much weight loss in response to orlistat. Poor compliance is always a factor in the variability that exists among studies of the same compound. Another reason for these discrepancies is that orlistat users are warned to avoid excess ingestion of dietary fats, and are likely to switch to consuming more simple carbohydrates. Overweight individuals often suffer metabolic disturbances, meaning that ingested sugars more readily convert to stored (triglyceride) fats on the body. This is why taking carbohydrate-blocking agents (alpha-glucosidase and amylase inhibitors) in conjunction with orlistat for the first 60 days of a weight-loss program may be necessary to induce some immediate reduction of fat pounds that overweight and obese individuals expect.

Orlistat is available by prescription in 120 mg capsules as Xenical®, or over-the-counter under the trade name alli® in 60 mg capsules. The suggested dose for the 60-day initiation period is 120 mg before each meal (three times a day). Make sure to take fat-soluble nutrients such as omega-3 fish oil, vitamins D, E, and K, and carotenoids (like lutein and zeaxanthin) at the time of the day most removed from the last orlistat dose as its fat-blocking effects can interfere with absorption of these critical nutrients into the blood.

Pillar Number 9: Eat to Live a Long and Healthy Life

No one should embark on a weight-loss program by trying to follow a fad diet that cannot be adhered to over the long term. At the same time, aging individuals have to make choices as to what is more important, i.e., ingesting foods that are known to promote weight gain (and cause horrendous diseases) or selecting healthier foods that facilitate weight loss and protect against illness.

Conclusion

Six years ago, Life Extension® published an article about the dangers of eating foods cooked at high temperatures (over 250 degrees). Overcooked foods damage our body’s proteins, while foods cooked at lower temperatures have been shown to facilitate weight loss. So just changing how your foods are prepared could help you shed body fat and, at the same time, protect against age-related disease (see “Eating food cooked at high temperature accelerates aging,” Life Extension, May 2003).

Solid scientific evidence shows that excess calorie ingestion accelerates the onset of degenerative disease and the aging process itself—in addition to promoting the unsightly accumulation of body fat. With the help of the various elements described in this Nine Pillars of Successful Weight Loss, the reduction in body fat one may see should provide a strong motivational basis to initiate more sensible food intake patterns.

It’s never too late to change one’s lifestyle in a manner that promotes better health while melting away excess body fat.

Conclusion

Lifestyle changes are clearly critical to safe and responsible loss of weight and body fat and provide additional quality-of-life benefits that vastly exceed simple reduction in disease risk. Clinicians and patients who are truly committed to attaining a long and happy life will always include responsible diet and moderate exercise programs in their long-term plans.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

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