Life Extension Magazine

Life Extension Magazine July 2011

Cover Story

Shed Pounds by Inhibiting Cellular Fat Storage

By Kirk Stokel

Shed Pounds by Inhibiting Cellular Fat Storage

Health authorities are warning about the devastating consequences of obesity, yet doctors remain in the dark about what causes people to accumulate so many fat pounds as they age.

Through a series of well-designed studies, scientists investigating certain plant extracts found they can block fat storage at the cellular level.

In a significant scientific advance, a potent new weapon has been identified to help safely induce weight loss.

This article describes how a novel dual plant extract favorably modulates six pathways that fat cells use to trigger weight gain.

When tested on humans in a placebo-controlled study, those taking this dual plant extract lost 4.05 inches of abdominal fat and dropped 11.4 pounds after eight weeks…with weight loss observed as early as 14 days.1

Cells that store fat are called adipocytes. They are deposited throughout our bodies.2,3

As we age, adipocytes tend to expand and congregate in areas that are cosmetically unsightly and detrimental to our health.

Of greatest concern are the adipocytes that deposit deep in our abdomens. This “visceral fat” represents more than fat stored on our waistlines. Visceral fat is chemically active tissue that churns out a torrent of pro-inflammatory cytokines.4

Those with bulging belly fat suffer constant bombardment from toxic cytokines that trigger the metabolic syndrome and its deadly consequences.5,6

This widespread problem led scientists to seek out plant extracts that specifically interfere with adipocyte fat storage in our abdominal anatomy.

Sphaeranthus indicus
Sphaeranthus indicus

How Unwanted Fat Storage Occurs

Excess calories transform to fat deposits in adipocytes7 through a multi-step process known as adipogenesis.

When fewer calories are consumed, fat is released from adipocytes to meet the body’s energy needs.8,9 This is known as lipolysis.

A dual plant extract has been studied based on its ability to simultaneously inhibit adipogenesis (fat storage) and enhance lipolysis (fat breakdown and release).

Mangosteen fruit
Mangosteen fruit

Like any other cell, adipocytes develop from undifferentiated stem cells. Premature, developing fat cells are called pre-adipocytes. When you ingest more calories than your body needs, “young” pre-adipocytes respond by maturing into “adult” adipocytes.7,10-12

“Adult” adipocytes take up excess fatty acids from your bloodstream and begin expanding. It is this process of fatty acid uptake and adipocyte expansion that ultimately results in obesity and its pathologic consequences. Every excess calorie contributes to the maturation and growth of fat cells in this way. Past a certain point, adipocytes distend and become bloated, much in the same way your belly does.

Not all adipocytes are the same. While fat cells distribute throughout your body, those that store in your abdomen—producing so-called visceral fat or belly fat—are more than just storage “containers.”

Belly fat cells are chemically active. They form fatty tissue capable of releasing detrimental pro-inflammatory cytokines.4

In obese individuals, the mass of excess visceral fat deposits generates a pro-inflammatory flood of cytokines. This cytokine release then incites a cascade of harmful effects that, if left unchecked, contributes to the onset of multiple degenerative diseases.5,6

So unwanted body fat storage happens when pre-adipocyte stem cells mature in order to store excess dietary fat (adipogenesis) while the ability to break down stored fat (lipolysis) diminishes.

What You Need to Know: Inhibiting Cellular Fat Storage
Inhibiting Cellular Fat Storage
  • An obesity epidemic continues to rage in this country, with more than two-thirds of the American population overweight or obese.
  • Conventional medicine has yet to offer any safe, long-term, practical solution.
  • Cutting-edge researchers continue to identify novel natural weight loss—inducing agents.
  • Among the most recent is a dual plant extract containing extracts of the flower S. indicus and the mangosteen fruit, both native to Asia.
  • When combined, the resulting dual extract blend was found to favorably influence six distinct biomolecular pathways by which fat cells trigger weight gain. In placebo-controlled clinical trials involving obese subjects, this dual extract safely induced total weight loss of 11.4 pounds, a decline of 2.05 in body mass index (BMI), and a reduction of 4.05 inches in harmful visceral fat after just eight weeks.1

Combating Surplus Body Fat Storage

Searching for natural interventions that would effectively inhibit fat accumulation (adipogenesis) and enhance fat burning (lipolysis), scientists evaluated more than a thousand plants for evidence that would meet this criteria.13

Two plants whose extracts demonstrated significant biological effects were:

  1. Sphaeranthus indicus flower (S. indicus)13
  2. Mangosteen fruit (Garcinia mangostana).13
Control adipocyte cells not treated with S. indicus display lipid accumulation.
Control adipocyte cells not treated with S. indicus display lipid accumulation.
Adipocyte cells treated with S. indicus inhibited fat accumulation.
Adipocyte cells treated with S. indicus inhibited fat accumulation.

In the laboratory, S. indicus and mangosteen extracts powerfully impeded adipogenesis.

When cells were treated with S. indicus alone, fat storage was inhibited by as much as 65%, compared with control cells. Photographs (below) show a markedly visible difference between the two cell groups. The control cells show a bloated, “foamy” appearance, bulging with fat droplets, compared to the smaller, more naturally contoured cells treated with the S. indicus extract.13

Each of these extracts also enhanced lipolysis (or fat burning), by as much as 56% compared to control cells.13

Having identified these unifying properties in the two extracts, the researchers set out to determine if they would exhibit enhanced effects when used in combination.

They found that the S. indicus and mangosteen extracts favorably modulate the activity of six genomic pathways involved in fat cell formation and breakdown.13

Remarkably, these extracts reduced gene expression that promotes adipogenesis while favorably influencing a gene involved in desirable lipolysis.

The box on this page shows how these plant extracts, used alone and in combination, positively modulated the markers involved in unwanted cellular fat accumulation by inhibiting adipogenesis and promoting lipolysis.

Given these observations, researchers recognized that this novel blend of plant extracts could result in significant weight loss via three distinct mechanisms:

  1. Preventing “young” fat cells (pre-adipocytes) from developing into “mature” fat cells (adipocytes);
  2. Reducing the amount of fatty acids adipocytes could absorb;
  3. Speeding breakdown of bloated adipocytes’ existing fat stores.

The next step was to determine if these plant extracts would induce weight loss in experimental animals and—more importantly—obese humans.

Preventing Obesity in Rodents

When young adult rats are fed a high-fat diet they rapidly gain weight—just as humans often do.

To investigate the effects of the plant extracts that worked in cell studies, scientists fed a group of young adult rats a high-fat diet. Half the rats received the dual plant extract while the other half served as the control group.13

At the end of eight weeks, the control group rapidly gained weight. The rats fed a high-fat diet and given the dual plant extract, on the other hand, reduced body weight gain by an impressive 700%.13

This is not surprising considering these same plant extracts blocked fat accumulation by 48.5% and 65.9% in the cellular model.13

This study demonstrated that these plant extracts decrease diet-induced obesity in young adult rats. The real challenge, however, is whether these same plant extracts are effective in humans who are already obese.

How These Plant Extracts Combat Adipocyte Overload

The novel blend of S. indicus and mangosteen extracts inhibit expansion of new fat cells while promoting breakdown of lipids in existing adipocytes. Laboratory studies demonstrate the following molecular mechanisms that enable these two plants to combat adipocyte overload:

1. Adipocyte differentiation-related protein (ADRP): Stimulates lipid accumulation and lipid droplet formation in fat cells.13,14 Reducing levels of ADRP is considered a novel strategy for preventing or reducing dangerous fat accumulation, especially in the liver.12,13,15,16

2. Adipocyte fatty acid binding protein 4: Also known as aP2, this transports fatty acids into fat cells for storage. Increased levels of aP2 are associated with lipid profile abnormalities that lead to atherosclerosis; they may also be an independent risk factor for metabolic syndrome and cardiovascular disease.8,11,17-25

3. Perilipin: A protein that coats lipid droplets in adipocytes, thereby protecting their fat contents from being broken down. Inhibiting perilipin thus promotes lipolysis, contributing to a reduction in adipocyte fat content.9,26-28

4. Plasminogen activator inhibitor-1 (PAI-1): Produced primarily by endothelial (artery-lining) cells, PAI-1 plays a key role in blood clot formation and breakdown.29 It is also secreted by adipose tissue.30 High levels of PAI-1 thus correlate directly with abdominal obesity, body weight, and body mass index or BMI.31 In the presence of this novel plant extract blend, PAI-1 levels were ultimately found to decline significantly.1

5. PPAR-gamma (peroxisome proliferator-activated receptor-gamma): A primary metabolic “sensor” that triggers adipogenesis in the presence of excess calories.32 Reducing PPAR-gamma activity helps prevent fat cells from becoming bloated and dysfunctional. 7,9,14,33-36

6. Beta-3-adrenergic receptor (3AR): Gene expression for this recently discovered receptor was increased by the dual plant extract. It regulates fat breakdown (lipolysis) when an energy boost is needed. Switching on the beta-3 receptor spontaneously and dramatically increases fat cells’ energy expenditure, burning up unused fat in the process.6,37-41

Researchers have demonstrated that the six genomic pathways involved in fat cell formation and breakdown (described above) are favorably modulated when exposed to S. indicus and mangosteen extracts.17 This provides a scientific basis to explain the anti-obesity effects observed in human clinical trials.

Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.
Chart 1
Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.
Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.
Chart 2
Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.

Weight Loss Findings in Humans

Human weight loss studies comprise an active arm that received the potentially effective fat-reducing agent and a similar group that received an inactive placebo.

To evaluate the effects of these two plant extracts, 60 obese adults were recruited and divided into two groups. One arm of 30 patients functioned as the placebo group while a second group of 30 patients received 800 mg per day of a combination of the two plant extracts. Both groups followed a 2,000-calorie- per-day diet and were asked to walk 30 minutes five days a week.

At the end of eight weeks, the group receiving the two plant extracts showed the following improvements:1

  1. Reduction in total body weight of 11.4 pounds. This was 3.7 times greater than the placebo group.
  2. Reduction of 4.05 inches in the abdomen. This was 2 times greater than the placebo group.
  3. Reduction in body mass index (BMI) of 2.05. A decrease 3.9 times greater than the placebo group.

This was a randomized, double-blind, placebo-controlled study, the kind the FDA mandates before it approves new drugs. The charts on this page reveal the magnitude of the weight loss and belly fat reduction that occurred in the group receiving the dual plant extract compared to placebo.1 (See Charts 1 and 2)

In addition to the favorable results seen at eight weeks, researchers were impressed with the reduction in waist and hip circumference, as well as lost body weight that occurred within the first 14 days! In fact after only two weeks, the average weight reduction was 4.6 pounds.1

At eight weeks, the dual plant extract group showed reduction in the waist-to-hip ratio that was 2.2 times greater than the placebo group. This is an important improvement as it indicates dangerous visceral belly fat is being lost.

These findings are supported by a second, similarly designed trial involving 60 obese subjects. They were divided into three groups that consisted of a placebo arm, an active arm receiving one plant extract, and another active arm that received a dual plant extract. All participants followed a 2,000-calorie-per-day diet and were asked to walk for 30 minutes five times a week for 8 weeks.13

After eight weeks the group receiving the dual plant extract experienced statistically significant changes in their abdominal circumference, total body weight, and hip circumference similar to those seen in the first study mentioned above.13

These confirmatory findings indicate that this novel dual plant extract may enable aging humans to safely shed unwanted body fat stores. No major adverse events or side effects were reported in either study.

Protection against Coronary Thrombosis

Most sudden death heart attacks occur when a blood clot forms in a coronary artery, choking off oxygenated blood to a portion of the heart muscle.

A protein called plasminogen activator inhibitor-1 (PAI-1) inhibits the normal breakdown of arterial blood clots.29 High levels of PAI-1 are observed in obese individuals and are associated with increased heart attack risk.30,31

When studying the dual plant extract, researchers measured serum levels of plasminogen activator inhibitor-1 (PAI-1). Those receiving the dual plant extract showed a 24.3% reduction in dangerous PAI-1 levels, while the placebo group showed a 2.4% increase.1 (See Chart 3)

Those supplemented with the dual plant extract had a 60% drop in triglyceride levels compared to baseline.1

Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.
Chart 3
Adapted from: FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011 - Program No. 601.9, Poster No. A278.

Subjects given the dual plant extract increased levels of the key metabolic hormone adiponectin.1 Adiponectin regulates how much sugar is in your bloodstream and how quickly your body breaks down fat. In terms of fat loss, high adiponectin levels are desirable. Higher levels of adiponectin are associated with decreased deposits of body fat and a reduced susceptibility to diabetes and metabolic syndrome.42

The dual plant extract group showed trends toward reduced glucose and cholesterol, which are expected to occur in response to loss of belly fat and body weight.1

The loss of visceral fat in the dual extract group— 4.05 inches, amounting to twice the decline observed in the placebo group—is compelling.1 This is important because visceral fat releases a storm of pro-inflammatory cell-signaling molecules. Excess visceral fat is a known risk factor for a number of serious health threats, ranging from systemic inflammation to increased risk of hypertension, atherosclerosis, type 2 diabetes, and coronary artery disease.43-45

Taken together, these findings indicate markedly reduced vascular disease risk in obese individuals taking 800 mg a day of this dual plant extract.

Summary

Obesity arises from the increased size of individual adipocytes (fat cells) due to enhanced lipid (fat) accumulation. It worsens as greater numbers of pre-adipocytes transform into dysfunctional, bloated adipocytes.

The novel blend of plant extracts described in this article favorably influences six distinct pathways by which fat cells trigger weight gain.

In cell culture, these plant extracts reduce the ability of progenitor fat cells (pre-adipocytes) to transform into bloated fat cells. These studies also show that components of this dual plant extract reduce the amount of fatty acids taken up by adipocytes (adipogenesis) and facilitate the breakdown (lipolysis) of fat stored in existing adipocytes.

In a placebo-controlled clinical trial involving obese humans, this blend of S. indicus and mangosteen plant extracts safely induced weight loss of 11.4 pounds, along with a decline of 2.05 in body mass index (BMI) and a reduction of 4.05 inches in harmful visceral fat.1

While our medical establishment has failed to offer any safe, long-term, practical solutions for today’s obesity epidemic, natural agents are now available that substantively augment the effects of a sensible weight loss program.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1-866-864-3027.

Potent Anti-Diabetic Properties

Long prized in traditional Ayurvedic medicine for their weight loss-inducing properties, scientists confirmed that extracts from Sphaeranthus indicus (S. indicus) and the mangosteen fruit (Garcinia mangostana) exert an anti-diabetic effect in humans.

S. indicus has been used for centuries to combat diabetic symptoms, protect the liver, quell inflammation, boost mood, and aid in digestion.46

Diabetic lab animals treated with S. indicus extracts exhibit substantial reductions in blood glucose, along with enhanced liver and pancreatic function.47,48 In insulin-resistant mice, S. indicus extracts lower blood sugar and triglyceride levels while facilitating more efficient uptake of glucose in muscle tissue.49 Diabetic animals treated with S. indicus exhibit significantly lower levels of tissue oxidation,50 a major underlying factor in most life-threatening diabetic complications.48,49

The mangosteen is an edible fruit that grows throughout South Asia. Like S. indicus, parts of the fruit and its juice have been used for centuries to combat diabetes and obesity. One vital mechanism is its ability to block the critical metabolic enzyme alpha-amylase that breaks down starches into sugar.51 Alpha-amylase blockers limit the spike in blood glucose levels that would normally follow a carbohydrate-rich meal. Mangosteen extracts also inhibit enzymes involved in synthesizing fat molecules.33 It is this combination of blocking sugar uptake and blocking fat production that accounts in part for its weight loss—inducing properties.

Mangosteen extracts have an additional, noteworthy benefit. They have been shown to effectively limit the inflammation that typically accompanies fat cell accumulation.6,52 This inflammation contributes directly to insulin resistance. In one compelling study, levels of the inflammatory marker C-reactive protein declined significantly53 in obese individuals consuming mangosteen juice after only 8 weeks.

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