Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats
Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infus...
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| creator | Akirav, Eitan M. Chan, Owen Inouye, Karen Riddell, Michael C. Matthews, Stephen G. Vranic, Mladen |
| description | Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 μg · (kg body weight · d)−1; (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by ∼20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis. |
| doi_str_mv | 10.1016/j.metabol.2004.06.024 |
| format | Article |
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We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 μg · (kg body weight · d)−1; (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by ∼20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis.</description><identifier>ISSN: 0026-0495</identifier><identifier>EISSN: 1532-8600</identifier><identifier>DOI: 10.1016/j.metabol.2004.06.024</identifier><identifier>PMID: 15562400</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adrenocorticotropic Hormone - blood ; Animals ; Biological and medical sciences ; Blood Glucose ; Body Weight - drug effects ; Corticosterone - blood ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - metabolism ; Diabetes. Impaired glucose tolerance ; Eating - drug effects ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Epinephrine - blood ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Hyperphagia - blood ; Hyperphagia - drug therapy ; Hyperphagia - etiology ; Hypothalamo-Hypophyseal System - drug effects ; Hypothalamo-Hypophyseal System - metabolism ; Insulin - blood ; Leptin - pharmacology ; Male ; Medical sciences ; Mice ; Norepinephrine - blood ; Pituitary-Adrenal System - drug effects ; Pituitary-Adrenal System - metabolism ; Pro-Opiomelanocortin - biosynthesis ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid - biosynthesis ; Recombinant Proteins - pharmacology ; RNA, Messenger - biosynthesis</subject><ispartof>Metabolism, clinical and experimental, 2004-12, Vol.53 (12), p.1558-1564</ispartof><rights>2004 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-9cbd8c4f40f4af74956b8f482a517d8d80d4d18386d4cb5ae6ec73ec3446f59d3</citedby><cites>FETCH-LOGICAL-c391t-9cbd8c4f40f4af74956b8f482a517d8d80d4d18386d4cb5ae6ec73ec3446f59d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.metabol.2004.06.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16371337$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15562400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akirav, Eitan M.</creatorcontrib><creatorcontrib>Chan, Owen</creatorcontrib><creatorcontrib>Inouye, Karen</creatorcontrib><creatorcontrib>Riddell, Michael C.</creatorcontrib><creatorcontrib>Matthews, Stephen G.</creatorcontrib><creatorcontrib>Vranic, Mladen</creatorcontrib><title>Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats</title><title>Metabolism, clinical and experimental</title><addtitle>Metabolism</addtitle><description>Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 μg · (kg body weight · d)−1; (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by ∼20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis.</description><subject>Adrenocorticotropic Hormone - blood</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose</subject><subject>Body Weight - drug effects</subject><subject>Corticosterone - blood</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Eating - drug effects</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Epinephrine - blood</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Hyperphagia - blood</subject><subject>Hyperphagia - drug therapy</subject><subject>Hyperphagia - etiology</subject><subject>Hypothalamo-Hypophyseal System - drug effects</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Insulin - blood</subject><subject>Leptin - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Norepinephrine - blood</subject><subject>Pituitary-Adrenal System - drug effects</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>Pro-Opiomelanocortin - biosynthesis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glucocorticoid - biosynthesis</subject><subject>Recombinant Proteins - pharmacology</subject><subject>RNA, Messenger - biosynthesis</subject><issn>0026-0495</issn><issn>1532-8600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O1DAQhCMEYpeFRwD5ArcM7cRxMieEVvxJK8EBzlbH7kx6lMTB9uxqeBSeFo9mpD1ysix9Vd3VVRSvJWwkSP1-v5kpYe-nTQWgNqA3UKknxbVs6qrsNMDT4hqg0iWobXNVvIhxDwBt2-nnxZVsGl0pgOvi7w8MiXESE62JFxEoJh8wsV8ELzYQRopiPK4-jTjhzLZcOR04YTiW6AItWYs28T2no3gYeSLheOaF48jLTjwQ78YkJh-jwMWdnCisI-4Ys7-IKeS5_o9P3uavY-wpsRV5g_iyeDbgFOnV5b0pfn3-9PP2a3n3_cu32493pa23MpVb27vOqkHBoHBoc1rdd4PqKmxk6zrXgVNOdnWnnbJ9g6TJtjXZWik9NFtX3xTvzr5r8L8POb-ZOVqaJlzIH6LRrYRWqSaDzRm0IccJNJg18JwPYSSYUylmby6lmFMpBrTJpWTdm8uAQz-Te1RdWsjA2wuA0eI0BFwsx0dO162s6zZzH84c5XPcMwUTLdNiyXEgm4zz_J9V_gHtDbM3</recordid><startdate>20041201</startdate><enddate>20041201</enddate><creator>Akirav, Eitan M.</creator><creator>Chan, Owen</creator><creator>Inouye, Karen</creator><creator>Riddell, Michael C.</creator><creator>Matthews, Stephen G.</creator><creator>Vranic, Mladen</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20041201</creationdate><title>Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats</title><author>Akirav, Eitan M. ; Chan, Owen ; Inouye, Karen ; Riddell, Michael C. ; Matthews, Stephen G. ; Vranic, Mladen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-9cbd8c4f40f4af74956b8f482a517d8d80d4d18386d4cb5ae6ec73ec3446f59d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adrenocorticotropic Hormone - blood</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose</topic><topic>Body Weight - drug effects</topic><topic>Corticosterone - blood</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Eating - drug effects</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Epinephrine - blood</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Hyperphagia - blood</topic><topic>Hyperphagia - drug therapy</topic><topic>Hyperphagia - etiology</topic><topic>Hypothalamo-Hypophyseal System - drug effects</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>Insulin - blood</topic><topic>Leptin - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Norepinephrine - blood</topic><topic>Pituitary-Adrenal System - drug effects</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>Pro-Opiomelanocortin - biosynthesis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Glucocorticoid - biosynthesis</topic><topic>Recombinant Proteins - pharmacology</topic><topic>RNA, Messenger - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akirav, Eitan M.</creatorcontrib><creatorcontrib>Chan, Owen</creatorcontrib><creatorcontrib>Inouye, Karen</creatorcontrib><creatorcontrib>Riddell, Michael C.</creatorcontrib><creatorcontrib>Matthews, Stephen G.</creatorcontrib><creatorcontrib>Vranic, Mladen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolism, clinical and experimental</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akirav, Eitan M.</au><au>Chan, Owen</au><au>Inouye, Karen</au><au>Riddell, Michael C.</au><au>Matthews, Stephen G.</au><au>Vranic, Mladen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats</atitle><jtitle>Metabolism, clinical and experimental</jtitle><addtitle>Metabolism</addtitle><date>2004-12-01</date><risdate>2004</risdate><volume>53</volume><issue>12</issue><spage>1558</spage><epage>1564</epage><pages>1558-1564</pages><issn>0026-0495</issn><eissn>1532-8600</eissn><abstract>Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 μg · (kg body weight · d)−1; (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by ∼20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15562400</pmid><doi>10.1016/j.metabol.2004.06.024</doi><tpages>7</tpages></addata></record> |
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| subjects | Adrenocorticotropic Hormone - blood Animals Biological and medical sciences Blood Glucose Body Weight - drug effects Corticosterone - blood Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - metabolism Diabetes. Impaired glucose tolerance Eating - drug effects Endocrine pancreas. Apud cells (diseases) Endocrinopathies Epinephrine - blood Etiopathogenesis. Screening. Investigations. Target tissue resistance Hyperphagia - blood Hyperphagia - drug therapy Hyperphagia - etiology Hypothalamo-Hypophyseal System - drug effects Hypothalamo-Hypophyseal System - metabolism Insulin - blood Leptin - pharmacology Male Medical sciences Mice Norepinephrine - blood Pituitary-Adrenal System - drug effects Pituitary-Adrenal System - metabolism Pro-Opiomelanocortin - biosynthesis Rats Rats, Sprague-Dawley Receptors, Glucocorticoid - biosynthesis Recombinant Proteins - pharmacology RNA, Messenger - biosynthesis |
| title | Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats |
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