{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:49:49Z","timestamp":1783478989098,"version":"3.55.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Body weight loss of Lepob\/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) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ\/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ\/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol\/g) administered in 5- to 6-day intervals rectified the Lepob\/ob phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (\u223c25-fold) unmodified leptin was mandatory to achieve similar improvements.<\/jats:p>","DOI":"10.1210\/en.2015-1519","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T17:01:51Z","timestamp":1445533311000},"page":"233-244","source":"Crossref","is-referenced-by-count":29,"title":["Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lepob\/ob Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Florian","family":"Bolze","sequence":"first","affiliation":[{"name":"Lehrstuhl f\u00fcr Molekulare Ern\u00e4hrungsmedizin (F.B., A.B., N.R., S.M., M.K.) Technische Universit\u00e4t M\u00fcnchen, 85350 Freising-Weihenstephan, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Morath","sequence":"additional","affiliation":[{"name":"Else Kr\u00f6ner-Fresenius Center and ZIEL-Research Center for Nutrition and Food Science, and Munich Center for Integrated Protein Science and Lehrstuhl f\u00fcr Biologische Chemie (V.M., M.S., A.S.), Technische Universit\u00e4t M\u00fcnchen, 85350 Freising-Weihenstephan, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bast","sequence":"additional","affiliation":[{"name":"Lehrstuhl f\u00fcr Molekulare Ern\u00e4hrungsmedizin (F.B., A.B., N.R., S.M., M.K.) 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