PTP1B Research for Dummies and Why You Need To Know It

by Core Health Expert on July 14, 2009

in Leptin and Weight Loss

ScienceFairThe best of the newest weight loss science at a fourth grade level.

A significant amount of the newest science and research attempting to tackle America’s growing obesity problem is focused on hormonal disruptions and imbalances such as leptin resistance. LepToThin™ is natural science’s newest answer, in supplement form, to help address this issue. LepToThin™ contains LeptiPro™ which is the primary active ingredient to assist in improving leptin signaling. The main mechanism of action of this supplement occurs by inhibiting protein tyrosine phosphatase 1B, commonly known as (PTP1B). A plethora of research is currently being performed to assess the efficacy of PTP1B in the treatment of obesity, insulin resistance and leptin resistance.

To help your understanding of this ever-important concept and physiological cascade of events, I’ll provide a number of credible research excerpts followed by my ‘fourth grade version’ and interpretation. This should help you get to the bottom line on how and why this can significantly help you in your quest to lose weight naturally and improve your health.

Deal? Here we go…

labThe science says: In June of 2009, the medical journal, Molecular and Cellular Biology stated that:  neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues and downstream gene expression changes that promote leanness and increased energy expenditure. Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity is likely to involve coordinated regulation of AMPK in hypothalamus and peripheral tissues.

The interpretation: Inhibiting PTP1B may actually have an effect on the brain that would help you improve body composition and burn fat.

The science says: PTP1B Inhibitors:  (PTP1B) is a highly validated molecular target, which mediates insulin resistance in mammals. PTP1B dephosphorylates the insulin receptor (IR) thus blunting its ability to transduce signal upon insulin binding. Inhibitors of PTP1B would be expected to restore activity to the IR and thus would find therapeutic benefit in the treatment of diabetes.

The interpretation: Discovering and manufacturing PTP1B inhibitors are currently one of the ‘hot topics’ in the pharmacological approach to to finding a drug to address the obesity problem, which is a primary contributing factor to type 2 diabetes.

The science says: Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance.

The interpretation: When mice are fed a high fat diet it can increase the amount of PTP1B in the brain. A high fat diet possibly induced an overabundance of circulating leptin which leaves more leptin in the blood. The body then may become resistance to leptin’s effects; two of which are  regulating appetite and burning fat.

The science says: Neuronal PTP1B regulates adiposity, body weight and leptin action.

The interpretation: PTP1B has a big say in whether you store excess fat, how much you weigh and it also plays a pivotal role in the function of one of your master metabolic hormones-leptin.ptp1b-weight-loss

The science says: PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. PTP1B may be a novel target to treat leptin resistance in obesity.

The interpretation: PTP1B is present within the brain and effects the way that leptin is able to effect the brain. Mice that were devoid of PTP1B were literally resistant to obesity. One could extrapolate that with either the absence or decreased over-expression of PTP1B, leptin and insulin would both work more efficiently to regulate weight and metabolism. This study showed that PTP1B does in fact regulate leptin signaling.

The science says: Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of signaling by both of these hormones, so that inhibitors of this enzyme may provide promise for correcting endocrine abnormalities in both diabetes and obesity. As with other tyrosine phosphatases, identification of viable drug candidates targeting PTP1B has been elusive because of the nature of its active site. Beginning with novel phosphotyrosine mimetics, we have designed some of the most potent PTP1B inhibitors. However, their highly acidic structures limit intrinsic permeability and pharmacokinetics.

The interpretation: “We wish we could find something that inhibits PTP1B without so many side effects because if we could, we would make billions.”

As far back as 2002 analysts have estimated that an effective and safe drug targeting obesity could generate as much as $26 billion per year in the USA alone. “It is probably the largest pharmaceutical market ever, and carries with it 27–30 dangerous co-morbidities,” said Louis Tartaglia, vice president of metabolic diseases at Millennium Pharmaceuticals. If you add the patients who are obese and diabetic, the number soars even higher, as obesity and diabetes are linked diseases. (Some research says that as much as 80% of type 2 diabetes is related to obesity.


puzzleThe science says: Published studies demonstrate that the botanically derived phytochemical, isolated and purified single-peak Isoquinoline Alkaloid Berberine HCl, specifically and potently inhibits human Protein Tyrosine Phosphates 1B (PTP1 B).

The interpretation: LepToThin™ with LeptoPro™ was formulated to specifically and naturally improve the body’s ability to respond to leptin signaling, thus helping you become better able to lose weight.

References:

LepToThin review
Am J Physiol Endocrinol Metab 296: E291-E299, 2009
Nature Medicine12, 917 – 924 (2006)
Dev Cell. 2002 Apr;2(4):385-7.

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1 Heather 07.14.09 at 2:12 pm

Fascinating…will have to read the research!!!!!
Cheers

Heather’s last blog post..My Pendant Has Arrived!!!!!!!

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