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Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here, a single PAS(600)-Leptin injection (300 pmol·g(-1)) resulted in a maximal weight reduction of 21% six days after application. The negative energy balance of 300 kJ·(4 days)(-1) was driven by a decrease in energy intake whereas energy expenditure maintained stable. Mice that were food-restricted to the same extent only showed an energy deficit of 220 kJ·(4 days)(-1) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-Leptin contributes 75% to weight loss while the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-Leptin (100 pmol·g(-1)) administered in 5-6 days intervals rectified the Lep(ob/ob) phenotype. In total 16 nmol of PAS(600)-Leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia, glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-Leptin are substantiated by a comparison with previous studies in which around 400 nmol (∾25fold) unmodified leptin were mandatory to achieve similar improvements.
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Leptin resistance refers to states in which leptin fails to promote its anticipated effects, frequently coexisting with hyperleptinaemia. It is closely associated with obesity, and also observed in ph...
Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas le...
Endospanin 1 (Endo1), a protein encoded, in humans by the same gene than the leptin receptor (ObR), and increased by diet induced obesity, is an important regulator of ObR trafficking and cell surface...
Obesity is related to many major diseases and cancers. Women have higher rates of obesity and obesity is linked to commonly occurring cancers in women. However, there is a lack of knowledge of the uni...
Leptin is a hormone produced by adipose tissue that promotes satiety, and some evidence suggests that greater early life leptin exposure prevents excessive adiposity gain in later life. However, few s...
Our previous studies have demonstrated that there is substantial metabolic opposition to the maintenance of an altered body weight. Leptin is a protein secreted by fat cells and the circu...
We will assess the endocrine and immune effects of leptin replacement in leptin-deficient children, from a consanguineous Turkish family. We hypothesize that leptin replacement will have ...
This study will test the hypothesis that leptin contributes to the regulation of the dynamics of human endocrine function.
This is a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in patients who have completed a previous clinical trial on treatment with set...
This is a pilot and feasibility study to examine a novel intervention using leptin in weight-reduced individuals who have undergone bariatric surgery but still remain obese. Leptin, a pept...
Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.
A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.
An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.
One of the long-acting ANTIPSYCHOTIC AGENTS used for maintenance or long-term therapy of SCHIZOPHRENIA and other PSYCHOTIC DISORDERS.
A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes, hypertension and METABOLIC SYNDROME X.
Obesity is the condition in which excess fat has accumulated in the body (mostly in subcutaneous tissues). clinical obesity is considered to be present when a person has a BMI of over 30 (Oxford Dictionary of Medicine). It is becoming increasing common i...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...