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New drug sensitises leptin leading to weight loss

Discussion in 'Other Health News and Research' started by heapsreal, Apr 17, 2014.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    http://www.bariatricnews.net/?q=news/11357/new-drug-sensitises-leptin-leading-weight-loss

    A drug compound that increases sensitivity to the hormone leptin, thereby suppressing appetite, could have implications for the development of new treatments for obesity in humans. The study was published in the journal Cell Metabolism.

    "By sensitising the body to naturally occurring leptin, the new drug could not only promote weight loss, but also help maintain it," said senior study author George Kunos of the National Institute on Alcohol Abuse and Alcoholism. "This finding bodes well for the development of a new class of compounds for the treatment of obesity and its metabolic consequences."

    Although leptin is an appetite suppressant, leptin supplements alone have not been effective at reducing body weight in humans. It is believed that the human body becomes desensitised to the hormone over time, lessening its response.

    Researchers do not know why desensitisation occurs; however, it has been hypothesised that cannabinoid receptors, which mediate the feelings of hunger produced by cannabis and naturally occurring cannabinoids in the body, are involved in the process.

    In this study, investigators tested a new compound, JD5037, which targets cannabinoid receptor type 1 (CB1R) without penetrating the brain. They report that not only did JD5037 suppress the appetite of obese mice leading to weight loss, it also improved metabolic health.

    Appetite and weight reduction caused by JD5037 are mediated by resensitising mice to endogenous leptin through reversing the hyperleptinemia by decreasing leptin expression and secretion by adipocytes, and increasing leptin clearance via the kidney.

    Importantly, the mice did not show signs of anxiety or other behavioural side effects.

    Previously, researchers have concentrated on blocking these receptors believing it could be more effective at long-term weight loss and developed anti-obesity drugs that target CB1R. However, only one CB1R-binding drug (rimonabant) was sold in Europe beginning in 2006 and it was taken off the market a few years later due to serious psychiatric side effects, including anxiety, depression and thoughts of suicide.

    In order to reduce these side-effects, Kunos and his team developed a CB1R-targeting drug that did not enter the brain as easily as rimonabant. However, the drug was not as effective at reducing weight and improving metabolic health, possibly because of its specific mode of action.

    “This study shows that inverse agonism at peripheral CB1R not only improves cardiometabolic risk in obesity but has anti-obesity effects by reversing leptin resistance,” said Kunos. “Obesity is a growing public health problem, and there is a strong need for new types of medications to treat obesity and its serous metabolic complications, including diabetes and fatty liver disease.”
     
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  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    JD5037 is an antiobesity drug candidate which acts as a peripherally-restricted cannabinoid inverse agonist at CB1 receptors. It is very selective for the CB1 subtype, with a Ki of 0.35nM, >700-fold higher affinity than it has for CB2 receptors.[1]

    In animal studies, JD5037 does not readily cross the blood brain barrier and thus is not expected to produce the psychiatric side effects in humans which led to the withdrawal of rimonabant from the market. Its antiobesity effects are believed to be mediated by blockade of peripheral CB1 receptors, resulting in decreased leptin expression and secretion and increased leptin clearance by the kidneys. In obese mice given the drug, the resulting resensitization to leptin levels produced decreased food intake, weight loss, and normalized responses to glucose and insulin.

    JD5037 is covered in the following US Patents issued to Jenrin Discovery: 8,088,809 (1/3/12) ), 7,666,889 (2/23/10), 7,482,470 (1/27/09). The synthesis of JD-5037 and related analogs along with structure activity relationships has been reported.[2]

    A review on the approaches and compound types being pursued as peripherally restricted CB1 receptor blockers, including JD5037, has been published. [3]

    http://en.wikipedia.org/wiki/JD5037
     
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  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Metformin Restores Leptin Sensitivity in High-Fat–Fed Obese Rats With Leptin Resistance
    1. Yong-Woon Kim1,
    2. Jong-Yeon Kim1,
    3. Yong-Hoon Park2,
    4. So-Young Park13,
    5. Kyu-Chang Won4,
    6. Kwang-Hae Choi2,
    7. Jung-Yoon Huh1 and
    8. Ki-Hak Moon5
    +Author Affiliations

    1. ywkim@med.yu.ac.kr

    Next Section
    Abstract
    To evaluate whether metformin enhances leptin sensitivity, we measured leptin sensitivity after 4 weeks of metformin treatment (300 mg/kg daily) in both standard chow and high-fat–fed obese rats. Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 μg daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat–fed obese rats compared with age-matched standard chow rats. However, these responses to leptin were corrected by metformin treatment in high-fat–fed obese rats. Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat–fed obese rats. The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. In an acute study, metformin treatment also increased the anorexic effect of leptin (5 μg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat–fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.

    http://diabetes.diabetesjournals.org/content/55/3/716.full
     
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  4. minkeygirl

    minkeygirl Narcissism = lack of self awareness

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    I saw a report on tv a few years ago having to do with sleep and leptin. The had college students stay up late and not get enough sleep and they all pigged out and gained weight. The sleep deprivation turned on (or off) the leptin which works on appetite (sorry couldn't read that entire thing @heapsreal) so they gained weight.

    There are even books on Amazon using the Leptin Diet. I know when I am sleep deprived I eat non stop and am still hungry.
     
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  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Its a big massive web of leptin, insulin sensitivity, sleep, circadian rthym, sex and adrenal hormones, dopamine etc that all tend to feed off each other. complicated mess i think alot of us have??
     
  6. minkeygirl

    minkeygirl Narcissism = lack of self awareness

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    I agree. I saw that thing a few years ago too so it's not a new thing.
     
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