Sesamin - Bye, Bye Fatty!

When one diets to lose fat, it is relatively easy to lose those first 5-10 pounds of fat. After that initial stage of fat loss, the body begins to make it harder to lose more fat and easier to regain fat by reducing the concentrations of "fat-burning" enzymes and up-regulating the "fat storage" enzymes.

These changes in enzyme activity play a big role in the cessation of fat loss and lack of progress experienced by dieters. The body wants to function in a specific range of body fat referred to as the body's "set point." The body functions optimally at its set point level of body fat and therefore attempts to keep its fat storages at this set point.

In an attempt to override the bodies desire to keep its fat storage near its set point, dieters often take weight loss supplements, such as thermogenics. The problem with most weight loss supplements is they do nothing to override the body's desire to stop fat loss and merely provide a means to boost one's metabolism for a short while.

While such a supplement may help one lose a little more fat, they are only a short-term solution for dieters. Thermogenics, such as ephedrine, aid in fat loss by causing fat cells to release fatty acids. The body has a fixed capacity for fat loss and if enzyme activity has been shifted to promote fat storage over fat oxidation, releasing fatty acids from fat cells will be of little use if they cannot be oxidized.

In order to successfully lose fat, one must create a stimulus that tells the body to burn more fat and to stop storing/trying to store fat. Sesamin, a lignan found in sesame seeds, has been shown to do just that - make the body oxidize more fat and increase its capacity to do so while decreasing the storage of fat.

Sesamin & The Peroxisome Proliferator-Activated Receptors (PPAR)

Sesamin is a lignan isolated from sesame seeds. A lignan is a molecule that combines with another entity acting as an "activator." In the case of sesamin, it binds to and activates a receptor called Peroxisome Proliferator-Activator Receptor Alpha (PPARalpha).

The PPAR receptor family is divided into three subgroups:

1. Alpha

2. Delta

3. Gamma

Peroxisome Proliferator-Activator Receptor Alpha

PPARalpha is highly expressed in muscle, the liver, kidneys, and heart and is involved in the regulation of lipid metabolism, specifically the transcription of the genes involved in the beta-oxidation (burning) of fatty acids and lipogenesis.

	Fat Metabolism! Dietary fat is not an enemy. In fact, when adequate amounts of good fats (unsaturated) are consumed, it can improve one's health and athletic performance. Learn what these good fats are and how they keep the body function properly. [ Click here to learn more. ]

Activation of PPARalpha increases gene expression of the fatty acid oxidation enzymes and decreases gene expression of lipogenic enzymes. Sesamin has been shown to be a potent PPARalpha activator¹.

Sesamin, Mitochondria, Peroxisomes, & Beta-Oxidation

Fat can be oxidized in the mitochondria and the peroxisomes of cells, the majority of this oxidation occurring in skeletal muscle cells and the liver. PPARalpha activation by sesamin increases fat oxidation in mitochondria and peroxisomes by increasing the expression of enzymes involved in beta-oxidation of fatty acids⁹.

	Mitochondria & Peroxisomes Two Major organelles of the human cell. Mitochonidria: The spherical or elongated organelles in the cytoplasm of nearly all eukaryotic cells, containing genetic material and many enzymes important for cell metabolism, including those responsible for the conversion of food to usable energy. Also called chondriosome. Peroxisomes: These function to rid the cell of toxic substances, such as hydrogen peroxide, or other metabolites and contain enzymes concerned with oxygen utilization such as D-amino acid oxidase and urease oxidase. Peroxisomes were discovered by Christian de Duve in 1965.

Of vital importance, Sesamin increases the expression of the mitochondrial enzyme carnitine palmitoyl transferase (CPT)⁹. CPT, the rate-limiting enzyme in beta-oxidation of fatty acids in skeletal muscle and liver cell mitochondria, is found on the outer membrane of mitochondria and carries fatty acids across the membrane into the mitochondria by binding to them.

Increasing the expression of CPT will allow more fatty acids to be transported into the mitochondria where they can be oxidized.

Sesamin's ability to cause an increase in fatty acid oxidation in both the mitochondria and peroxisomes is important because mitochondria can only oxidize short-chain to long-chain-fatty-acids while peroxisomes can shorten fatty acids of all lengths, including very-long-chain-fatty-acids (VLCFA).

More Peroxisomes

As its name suggests, Peroxisome Proliferator-Activator Receptor cause the creation of additional peroxisomes. More peroxisomes means more fat can be oxidized.

PPARalpha activation also increases uncoupling-proteins (UCPs). UCPs decrease the efficiency of mitochondria, which means an increase in UCPs would increase the calories needed to produce the same amount of energy, as before, this is known as "calorie wasting."

"Wasting" calories would lead to a greater caloric expenditure and therefore fat loss. Through increasing the expression of the enzymes involved in beta-oxidation and increasing UCPs, PPARalpha activation by sesamin will increase the rate and capacity at which cells can burn fat.

Sesamin & Lipogenesis

In addition to increasing the oxidation of fat, Sesamin supplementation has also been shown to decrease lipogenesis (fat storage) by decreasing lipogenic enzymes in the liver.

Sesamin has been shown to decrease the lipogenic gene expression of sterol regulatory element binding protein-1 (SREBP-1), acetyl-CoA carboxylase, and fatty acid synthase, among other lipogenic enzymes¹⁰, which means less fat is esterifized in the liver and therefore less fat is stored in adipose tissue (fat cells).

So Sesamin works in two ways to make you lean (and keep you lean):

1. Increasing fat oxidation

2. Decreasing fat storage

Sesamin & Ketogenesis

Ketogenesis occurs when fatty acid oxidation is increased to a point where the liver cannot metabolize off the fatty acids for energy. Excess acetyl-CoA (which can be created from fat, glucose, or amino acid metabolism) is converted to ketones in the liver and released into the bloodstream to be used by other tissues (specifically the brain).

Ketogenesis is very important during low carb diets because the brain cannot use fatty acids for fuel, it can only use glucose. When glucose is low, the brain will turn to ketones for its energy.

Sesamin has been shown to increase ketone production¹¹. Increasing ketone production should have protein-sparing effect as less amino acids will be needed to create ketones. This means your muscle mass will be spared while dieting.

Health Benefits Of Sesamin

In addition to increasing fat oxidation and decreasing lipogensis, Sesamin supplementation also has many health benefits. Sesamin has been shown to:

• Be antihypertensive³

• Be an antioxidant itself and increase the recycling of vitamin E⁴

• Provide liver protection against alcohol and improve liver function⁵

• Decrease cholesterol levels⁶, while increasing high density lipoprotein (HDL aka "good cholesterol") levels⁷

• Be an anti-inflammatory⁸.

These health benefits alone make Sesamin supplementation a wise decision.

Supplementing With Sesamin

The sesamin content of sesame seeds and sesame oil is very low, meaning you would have to eat a TON of seeds/oil before you get even close to obtaining enough sesamin to reap its benefits.

Luckily, concentrated sesamin is commercially available.

Sesamin "Point-Blank" Summary

Sesamin supplementation will prime your body to oxidize fat and not store it. Sesamin supplementation should also help spare muscle mass while dieting and has many positive health benefits.

Sesamin:

• Increases thermogenesis
• Increases fat oxidation
• Up-regulates "fat-burning" enzymes
• Decreases fat storage
• Down-regulates "fat-storage" enzymes
• Increases insulin sensitivity
• Increases ketone formation
• A fuel used when dieting
• Spares glucose
• Potent antioxidant
• Cholesterol reducer
• Increases HDL levels
• Decreases LDL levels
• Decreases blood pressure (antihypertensive)
• Improves liver and kidney health
• Anti-inflammatory
• No stimulant effect

References:

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• Biochim Biophys Acta. 2004 Jun 1;1682(1-3):80-91

• J Hypertens. 2004 Dec;22(12):2329-38

• Mol Cell Biochem. 2004 Jul;262(1-2):195-202

• Ann Nutr Metab. 1993;37(4):218-24

• J Lipid Res. 1991 Apr;32(4):629-38

• Clin Exp Pharmacol Physiol Suppl. 1995 Dec;22(1):S310-2

• Am J Clin Nutr. 2000 Sep;72(3):804-8

• J Agric Food Chem. 2001 May;49(5):2647-51

• Biochim Biophys Acta. 2001 Nov 30;1534(1):1-

1. J Nutr Sci Vitaminol (Tokyo). 1999 Aug;45(4):437-48