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Has anyone who has used MTII or Melanotan experienced fatloss that they can attribute to use of the peptide?
Responsiveness to Peripherally Administered Melanocortins in Lean and Obese Mice, Susann Bluher, Diabetes, Vol. 53, January 2004
The melanocortin pathway, one of the direct targets of leptin action in the brain (1), plays an important role in energy homeostasis. Mice with targeted deletion of the pro-opiomelanocortin (POMC) gene (2) or the melanocortin 4 receptor (MC4R) gene develop obesity associated primarily with hyperphagia and hyperinsulinemia (3). In addition, MC3 receptor knockout mice have increased fat mass and reduced lean body mass, but normal food intake, suggesting defects in energy partitioning (4).
Peripheral or central administration of the synthetic nonspecific melanocortin receptor agonist melanotetan II (MTII) to fasted or neuropeptide Y (NPY)-treated mice as well as obesity-prone or genetically obese animals, such as Sprague-Dawley rats or rhesus macaques, acutely and chronically suppresses food intake and increases sympathetic nervous system activity (5–9), whereas melanocortin antagonism has opposite effects (10 –13). We recently reported that MTII treatment decreases body weight, primarily by suppressing food intake and secondarily by increasing energy expenditure, and improves insulin resistance in mice (14). However, the mechanisms underlying improvement of weight loss and insulin resistance, as well as the development of tachyphylaxis after prolonged MTII administration, remain largely unknown.
Results
In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant and leptin-sensitive mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in [obese] mice than in lean mice; 3) the tachyphylactic effect [loss of effect] after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY [Neuropeptide Y] and AgRP mRNA levels [adiponectin receptor], whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.
The melanocortin pathway, one of the direct targets of leptin action in the brain (1), plays an important role in energy homeostasis. Mice with targeted deletion of the pro-opiomelanocortin (POMC) gene (2) or the melanocortin 4 receptor (MC4R) gene develop obesity associated primarily with hyperphagia and hyperinsulinemia (3). In addition, MC3 receptor knockout mice have increased fat mass and reduced lean body mass, but normal food intake, suggesting defects in energy partitioning (4).
Peripheral or central administration of the synthetic nonspecific melanocortin receptor agonist melanotetan II (MTII) to fasted or neuropeptide Y (NPY)-treated mice as well as obesity-prone or genetically obese animals, such as Sprague-Dawley rats or rhesus macaques, acutely and chronically suppresses food intake and increases sympathetic nervous system activity (5–9), whereas melanocortin antagonism has opposite effects (10 –13). We recently reported that MTII treatment decreases body weight, primarily by suppressing food intake and secondarily by increasing energy expenditure, and improves insulin resistance in mice (14). However, the mechanisms underlying improvement of weight loss and insulin resistance, as well as the development of tachyphylaxis after prolonged MTII administration, remain largely unknown.
Results
In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant and leptin-sensitive mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in [obese] mice than in lean mice; 3) the tachyphylactic effect [loss of effect] after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY [Neuropeptide Y] and AgRP mRNA levels [adiponectin receptor], whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.
Definitions of terms used:
Tachyphylaxis is a term used to describe a high intensity prolonged stimulus or often repeated stimulus which brings about a diminished response also known as desensitization.
Neuropeptide Y's main effect is increased food intake and decreased physical activity. NPY is secreted by the hypothalamus, and in addition to increasing food intake, it increases the proportion of energy stored as fat and blocks nociceptive signals to the brain.
Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults...
Tachyphylaxis is a term used to describe a high intensity prolonged stimulus or often repeated stimulus which brings about a diminished response also known as desensitization.
Neuropeptide Y's main effect is increased food intake and decreased physical activity. NPY is secreted by the hypothalamus, and in addition to increasing food intake, it increases the proportion of energy stored as fat and blocks nociceptive signals to the brain.
Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults...
