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Leptin!

bigrand

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Leptin Downregulates Specific Liver Enzyme Causing Leanness, Hypermetabolism




NEW YORK (Reuters Health) Jul 12 - Scientists at The Rockefeller University in New York report that they have identified a specific hepatic enzyme that is downregulated by the leptin gene, which leads to leaner animals that have more energy expenditure.
Suppression of RNA synthesis of hepatic stearoyl-CoA desaturase-1 (SCD-1) resulted in the changes, according to the report in the July 12th issue of Science by Dr. Jeffrey M. Friedman and colleagues at Rockefeller and at the University of Wisconsin, Madison.

The team found that found that leptin-deficient (ob/ob) mice who were also deficient in SCD-1 had a 40% reduction in body mass and a 75% increase in energy expenditure compared with ob/ob controls who did not have a decreased expression of the SCD-1 gene. The SCD-1 deficient mice had very low triglyceride and VLDL cholesterol production and livers that were histologically normal.

Dr. Friedman notes that the metabolic effects of leptin cannot be explained by food intake alone, as the findings published today show. "These data show that SCD-1 is required for the fully developed obese phenotype of ob/ob mice and suggest that a significant proportion of leptin's metabolic effects may result from inhibition of this enzyme."

The investigators speculate that downregulation of the SCD-1 enzyme reduces fatty acid biosynthesis by reducing intracellular malonyl CoA and is also accompanied by an increase in fatty acid oxidation.

Science 2002;297:240-243.



I like the 75% increase in energy expenditure and 40% loss in mass. Leptin is a very interesting topic to me. Anyone know of any good info on how to manipulate it?
 
It was a very recent study sent to me from medscape.
I dont know much about Bromo, other than i heard it can act on Leptin somehow?
 
For you lazy bastards:

Leptin, a hormone-like messenger protein (known technically as a cytokine), is produced in relatively large amounts by fat tissue and in smaller amounts by other peripheral organs, and then secreted into the bloodstream, where it travels to the brain and other tissues, causing fat loss and decreased appetite. Once leptin has been secreted by your fat cells, it travels to the hypothalamus-the part of your brain that has an influence on eating behavior.

In the medial hypothalamus, leptin activates "anorectic" nerve cells, which serve to suppress your appetite.

At the same time, leptin prevents "orexigenic" cells from stimulating your appetite.

Leptin (from the Greek leptos, meaning thin) first came to national attention in 1994 when the obesity gene and its product leptin were discovered.

It was shown then that obese mice dropped 40 percent of their body weight after only one month of treatment with leptin.

Leptin also improved symptoms of diabetes. Recently, the taste organ was found to be one of the peripheral targets for leptin. The hormone specifically inhibits sweet taste responses in lean mice. Thus, leptin appears to act as a modulator of sweet taste.

Leptin also suppresses a gene that produces an enzyme known as acetyl-CoA carboxylase, or ACC, which is essential for fat production.


When researchers injected laboratory mice with leptin, previously obese mice became as thin as rodent track stars!

(Left) Mouse with defective ob gene lacks the OB protein (leptin), which regulates the body, signaling the amount of fat stored. (Right) Mouse treated with leptin shed 40 percent of its body weight. Both of these mice have a defect in a gene called obese (ob). This mutation usually results in a marked increase in the amount of fat.

Administration of the protein encoded by the ob gene, called leptin, reduced the body weight of the ob mice.

After four and a half weeks, the ob mouse on the left, which did not receive leptin, weighed approximately 67 grams while the mouse on the right, who received daily injections of leptin, weighed 35 grams. Normal mice weigh approximately 24 grams, a weight equivalent to that of an orange.

Daily injections of leptin to ob mice reduced body weight via effects on food intake and energy expenditure, meaning the treated animals ate less and also burned more calories.

Some researchers believe that leptin works, in part, by inhibiting the synthesis of fat in fat cells and increasing the burning of fat in muscle cells-that it works at an enzymatic cellular level.

Copyright © 2002 - ITG Inc. All Rights Reserved
ImmuneTree 1-888-484-8671

Karma anyone?

:) :) :)
 
Leptin and HGH

Read this carefully!!!





Lee-Benner Institute (LBI) research has uncovered a dramatic new hormone-like substance that reduces subcutaneous fat deposits. By sequencing a chain of amino acids at a protein producing laboratory, LBI has been able to create an oral analogue (similar in function, but not in origin or structure), of the anti-obesity hormone, leptin. This is a hormone that affects the brain’s appetite control center and can knock an average of 4 pounds off people in a month.

Serum leptin concentrations reflect the size of the subcutaneous fat depot better than total fat mass or abdominal visceral fat. At the initiation of puberty, there is a divergence in circulating leptin between boys and girls. In boys, leptin concentrations increase and then markedly decrease to prepubertal concentration levels. In girls, there are only increasing concentrations. It is believed these patterns are relevant to the markedly different alterations in the regional distribution of body fat that occurs in boys and girls at puberty.

Human obesity is more closely linked to leptin resistance than to the absence of leptin. Obese human patients do not have depleted leptin levels in their blood streams. In fact, the heavier the person, the higher the levels. Still, that does not rule out the idea that leptin might work as a fat-loss therapy. Patients with adult-onset diabetes make insulin, but develop a resistance to the insulin hormone that can sometimes be overcome by oral hypoglycemic agents.

In the same way, supplementing the new leptin analogue can override the relative resistance to the body’s own naturally produced leptin hormone.

Replacement therapy with human growth hormone (hGH) [Click here for information on Human Growth Hormone] makes the individual more sensitive to leptin therapy. Growth hormone significantly reduces intra-abdominal visceral fat. Leptin, used in concert with hGH, affects the total fat mass by significantly reducing subcutaneous fat deposits. When used without the benefit of hGH injections, leptin given alone to a group of people with a common variety of obesity was relatively ineffective in most of them.

However, the net effect of combining leptin with hGH replacement therapy is remarkable. The cosmetic appearance is as though a human lathe was applied to trim away unwanted fat deposits such as "love-handles", cellulite, and "saddle-bags". This occurs gradually over a few months period of use without any invasive, painful, and expensive surgery such as liposuction.
 
Shit, okay....
From what ive read, leptin is good, it will lead to fat loss.......
Prolactin is bad.
leptin produces prolactin?
Shit im confused.....
 
Shit im confused


You shouldn't be. As with most everything in life there is no free lunch. As another example, leptin decreases testosterone in rats (1). This may explain the link between decreased testosterone secretion and hyperleptinemia in obese men.

Also, there really hasn't been that much research on the effects of leptin in humans, and what there is is often contradictory. What happens in rats doesn't always happen in people.


(1) J Endocrinol 1999 May;161(2):211-8
Leptin inhibits testosterone secretion from adult rat testis in vitro.
Tena-Sempere M, Pinilla L, Gonzalez LC, Dieguez C, Casanueva FF, Aguilar E.
 
Test will decrease leptin in the blood, probably increases leptin sensitivity which is the key and may alter fat production of the hormone, possibly through myostatin regulation.

The myostatin gene regulates leptin secretion from fat. In myostatin knockout mice, leptin is reduced but the mice are leaner and more muscular.

If we could regulate myostatin, we'd all be huge and ripped. Juice would be obsolete.

It won't be long.

W6
 
Somebody in my lab is determining the atomic structure of leptin, but I don't know shit about it personally. But I can get the clones..........
 
Bromo is supposed to increase leptin isn't that what that new bromo book was about? isn't that why isnt so good for fat loss?
 
Bromo is supposed to increase leptin isn't that what that new bromo book was about


I was going to deliver my usual cynical diatribe, but just to surprise georgie24 I'll be more upbeat. I have not read Lyle McDonald's book but I don't think it is leptin that dopamine is supposed to be targeting. Rather, bromocriptine, a dopamine agonist, "can reverse many of the metabolic alterations associated with obesity by resetting hypothalamic circadian organization of monamine neuronal activities" to quote the researchers at Ergo Science who pioneered this research.

What these guys noticed was that if bromocriptine is given to animals that usually store fat and then hibernate, they no longer store fat. Evidently this circadian fat storage phenomenon is somehow regulated by dopaminergic neuronal transmission. Leptin is not involved because when bromocriptine is administered to obese mice engineered to lack leptin, the mice still lose weight.

The Ergo people reasoned that humans might have a similar mechanism of fat storage and tried it on people. It seemed to work. Here is the relevant abstract:


Diabetes Care 1996 Jun;19(6):667-70

Bromocriptine (Ergoset) reduces body weight and improves glucose tolerance in obese subjects.

Cincotta AH, Meier AH.

Ergo Science, Charlestown, Massachusetts 02129, USA.

OBJECTIVE: A double-blind placebo controlled study investigated long-term effects of Ergoset, a new quick release formulation of bromocriptine, on body weight, body fat, and glucose tolerance in a group (n = 17) of obese subjects who were instructed to follow a moderate hypocaloric diet. RESEARCH DESIGN AND METHODS: Obese individuals (> 25% body fat for men and > 30% body fat for women) were instructed to follow a calorie-restricted diet (70% of weight maintaining based on study entry weight) and were randomized to daily treatment with Ergoset (1.6-2.4 mg/day) or placebo at 0800 over an 18-week treatment period. Oral glucose tolerance tests were performed on subjects before initiation and again at termination of treatment. Body weight and body fat (determined by skinfold measurements) were quantified every 2 weeks during the course of treatment. RESULTS: Ergoset treatment for 18 weeks significantly reduced body weight and body fat versus placebo (6.3 +/- 1.5 and 5.4 +/- 1.1 kg vs. 0.9 +/- 1.0 and 1.5 +/- 0.6 kg. respectively, P < 0.01). Ergoset, but not placebo, also improved glucose tolerance (P < 0.02); the stimulated area under the oral glucose tolerance curve was reduced by 46% (from 121 +/- 23 to 64 +/- 32 mg.h-1.dl-1), while the stimulated area under the insulin curve was reduced by 30%. CONCLUSIONS: When combined with instruction to follow a moderate hypocaloric diet, Ergoset, but not placebo, improves glucose tolerance and promotes significant weight and body fat loss in obese subjects over an 18- week treatment period.
 
Well shit Nandi, im sorry but im not as educated in the topic as you are. Im not looking for a free lunch, just a better understanding of Leptin and how it works. I was confused as to if it was a good thing or a bad, but it seems to have its positives and negatives as well. Havent you ever been confuse, or are you too smart for that?
Im still in JC right now with some micro/chem/ect background, not a WHOLE lot, so ya think you could cut me a break?
8-)
 
Havent you ever been confuse, or are you too smart for that


I get confused all the time, especially when I expect things to make sense. Most of the time it seems like when things make sense your understanding of some process is too simplistic. Usually the cause of this is that you have been tricked into thinking that someone's explanation for a particular observation is the correct explanation when in fact it is really just a hypothesis. When someone comes along with a different explanation (hypothesis), the natural reaction is to think "Wait a minute, this contradicts everything I thought I knew before. Now I'm really confused."

If you want to simulate the effects of leptin while you are waiting for it to be approved, there are some things out there. Basically, leptin's two actions that have been thus far identified as promoting weight loss are appetite suppression and in increase in basal oxygen consumption reflecting an increase in metabolic rate (more fat burning). Meridia is pretty good at suppressing appetite, while T3 certainly increases basal metabolic rate (BMR). The disadvantage of T3 in raising BMR is that, unlike with leptin, it seems to come at the expense of lean body mass as well as fat mass. A little anabolic steroid thrown into the mix will solve that problem.
 
Bromo does not increase leptin (or at least that is not its main mechanism of action), rather Lyle proposes that it (or dopamine) mimicks leptin -- i.e. it lies downstream of leptin signalling and mediates its actions.

My opinion is that is a bit less important than Lyle argues -- basically, that it is just another one of the numerous signals involved in adipostatic control, which are influenced by leptin, thus while it mimicks some of its effects, it does not mimick all of them -- retention of LBM and increase in BMR above basal levels, being two of the more important actions it lacks vs. leptin.
 
Would using bromo in conjunction with a product like Avant's LeptiGenl be a good idea then? How about adding in T3?
 
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Using LeptiGen could allow a lower-dose use of Bromo. Increasing Leptin levels, will increase T-3/Thyroid output; however, T-3 can still be added, if wished.
 
<p><strong><img src="http://www.elitefitness.com/images/diet-drugs/pramlintide-metreleptin.jpg" alt="Pramlintide Metreleptin" width="300" height="447" hspace="10" align="right" /><a href="http://bodybuilding.elitefitness.com/pramlintide-metreleptin-diet-drug" target="_blank">Pramlintide & Metreleptin Injectable Diet Drug Combo Promotes Massive Weight Loss</a></strong></p> <p>Every new diet drug that comes out is supposedly the next big thing.  However, two new drugs have the potential to shake up the dieting industry. They are Pramlintide and Metreleptin and it appears they can help people drop more pounds than ever before.  And the best part is that they’ll work on burning fat without you having to lift a finger! </p> <p> Weight loss expert Dr. Ken Fujoka stated this fact when he said, “With these new medications, now we're getting what we call double digit weight loss. 10 percent and up.”  Fujoka continued by saying, “So now you're losing 20, 30, and 40 pounds of weight with these new weight loss medications, which really makes the doctor and the patient a lot happier.”</p> <p>The Pramlintide and Metreleptin combo drug that is allowing people to see these double digit losses in weight is made by a company called Amylin.  Their injectable drug doesn’t have a name yet, but it has proven to curb people’s appetites in clinical trials. </p> <p>Here's the link to the full article:</p> <p><a href="http://bodybuilding.elitefitness.com/pramlintide-metreleptin-diet-drug" target="_blank">Pramlintide & Metreleptin Injectable Diet Drug Combo Promotes Massive Weight Loss</a></p>
 
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