Intranasal Insulin Suppresses Systemic but Not Subcutaneous Lipolysis in Healthy Humans
Context:Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism.Objective:We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans.Design:Pl...
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| Published in | The journal of clinical endocrinology and metabolism Vol. 99; no. 2; pp. E246 - E251 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Oxford University Press
01.02.2014
Copyright by The Endocrine Society Endocrine Society |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-972X 1945-7197 1945-7197 |
| DOI | 10.1210/jc.2013-3169 |
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| Abstract | Context:Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism.Objective:We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans.Design:Placebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment.Setting/Participants/Intervention:Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally.Main Outcome Measures:In the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration.Results:In the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations.Conclusions:Our findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue. |
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| AbstractList | Context:Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism.Objective:We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans.Design:Placebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment.Setting/Participants/Intervention:Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally.Main Outcome Measures:In the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration.Results:In the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations.Conclusions:Our findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue. Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism.CONTEXTInsulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism.We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans.OBJECTIVEWe investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans.Placebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment. SETTING/PARTICIPANTS/INTERVENTION: Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally.DESIGNPlacebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment. SETTING/PARTICIPANTS/INTERVENTION: Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally.In the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration.MAIN OUTCOME MEASURESIn the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration.In the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations.RESULTSIn the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations.Our findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue.CONCLUSIONSOur findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue. Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism. We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans. Placebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment. SETTING/PARTICIPANTS/INTERVENTION: Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally. In the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration. In the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations. Our findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue. CONTEXT:Insulin infused into the central nervous system of rats suppresses lipolysis in white adipose tissue, indicating a role of brain insulin in regulating systemic lipid metabolism. OBJECTIVE:We investigated whether central nervous insulin delivery suppresses lipolysis in healthy humans. DESIGN:Placebo-controlled, balanced within-subject comparisons were performed in both a main and an independent corroborative experiment. SETTING/PARTICIPANTS/INTERVENTION:Two groups of healthy volunteers were examined at the German University Clinics of Lübeck and Tübingen, respectively, with molecular analyses taking place at Mt Sinai School of Medicine (New York, New York). The 14 healthy male subjects of the main study and the 22 women and 5 men of the corroborative study each received 160 IU of human insulin intranasally. MAIN OUTCOME MEASURES:In the main study, we measured systemic levels of free fatty acids (FFAs), triglycerides, and glycerol and the rate of appearance of deuterated glycerol as an estimate of lipolysis before and after intranasal insulin administration. We also analyzed the expression of key lipolytic enzymes in sc fat biopsies and measured blood glucose and glucoregulatory hormones. In the corroborative study, FFA concentrations were assessed before and after intranasal insulin administration. RESULTS:In the main experiment, intranasal insulin suppressed circulating FFA concentrations and lipolysis (rate of appearance of deuterated glycerol) in the absence of significant changes in circulating insulin levels. Lipolytic protein expression in sc adipose tissue was not affected. The corroborative study confirmed that intranasal insulin lowers systemic FFA concentrations. CONCLUSIONS:Our findings indicate that brain insulin controls systemic lipolysis in healthy humans by predominantly acting on non-sc adipose tissue. |
| Author | Wellnitz, Toni Buettner, Christoph Machleidt, Felix Scherer, Thomas Heni, Martin Sayk, Friedhelm Fritsche, Andreas Hallschmid, Manfred Iwen, K. Alexander Häring, Hans-Ulrich Preissl, Hubert Lehnert, Hendrik |
| AuthorAffiliation | Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany; Departments of Medicine and Neuroscience and Diabetes, Obesity and Metabolism Institute (DOMI) (T.S., C.B.), Icahn School of Medicine at Mt Sinai, New York, New York 10029; Department of Internal Medicine III (T.S.), Division of Endocrinology and Metabolism, Medical University of Vienna, 1090 Vienna, Austria; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry (M.He., H.-U.H., A.F.), Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM) (M.He., H.P., H.-U.H., A.F., M.Ha.), fMEG (Fetal Magnetoencephalography) Center (H.P.), and Department of Medical Psychology and Behavioral Neurobiology (M.Ha.), University of Tübingen, 72076 Tübingen, Germany; and German Center for Diabetes Research (DZD) (M |
| AuthorAffiliation_xml | – name: Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany; Departments of Medicine and Neuroscience and Diabetes, Obesity and Metabolism Institute (DOMI) (T.S., C.B.), Icahn School of Medicine at Mt Sinai, New York, New York 10029; Department of Internal Medicine III (T.S.), Division of Endocrinology and Metabolism, Medical University of Vienna, 1090 Vienna, Austria; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry (M.He., H.-U.H., A.F.), Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM) (M.He., H.P., H.-U.H., A.F., M.Ha.), fMEG (Fetal Magnetoencephalography) Center (H.P.), and Department of Medical Psychology and Behavioral Neurobiology (M.Ha.), University of Tübingen, 72076 Tübingen, Germany; and German Center for Diabetes Research (DZD) (M.He., H.P., H.-U.H., A.F., M.Ha.), 72076 Tübingen, Germany |
| Author_xml | – sequence: 1 givenname: K. Alexander surname: Iwen fullname: Iwen, K. Alexander organization: 1Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany – sequence: 2 givenname: Thomas surname: Scherer fullname: Scherer, Thomas organization: 2Departments of Medicine and Neuroscience and Diabetes, Obesity and Metabolism Institute (DOMI) (T.S., C.B.), Icahn School of Medicine at Mt Sinai, New York, New York 10029 – sequence: 3 givenname: Martin surname: Heni fullname: Heni, Martin organization: 4Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry (M.He., H.-U.H., A.F.),72076 Tübingen, Germany – sequence: 4 givenname: Friedhelm surname: Sayk fullname: Sayk, Friedhelm organization: 1Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany – sequence: 5 givenname: Toni surname: Wellnitz fullname: Wellnitz, Toni organization: 1Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany – sequence: 6 givenname: Felix surname: Machleidt fullname: Machleidt, Felix organization: 1Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany – sequence: 7 givenname: Hubert surname: Preissl fullname: Preissl, Hubert organization: 5Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM) (M.He., H.P., H.-U.H., A.F., M.Ha.), 72076 Tübingen, Germany – sequence: 8 givenname: Hans-Ulrich surname: Häring fullname: Häring, Hans-Ulrich organization: 4Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry (M.He., H.-U.H., A.F.),72076 Tübingen, Germany – sequence: 9 givenname: Andreas surname: Fritsche fullname: Fritsche, Andreas organization: 4Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry (M.He., H.-U.H., A.F.),72076 Tübingen, Germany – sequence: 10 givenname: Hendrik surname: Lehnert fullname: Lehnert, Hendrik organization: 1Department of Internal Medicine I (K.A.I., F.S., T.W., F.M., H.L.), Section of Experimental and Clinical Endocrinology, University of Lübeck, 23538 Lübeck, Germany – sequence: 11 givenname: Christoph surname: Buettner fullname: Buettner, Christoph email: christoph.buettner@mssm.edu organization: 2Departments of Medicine and Neuroscience and Diabetes, Obesity and Metabolism Institute (DOMI) (T.S., C.B.), Icahn School of Medicine at Mt Sinai, New York, New York 10029 – sequence: 12 givenname: Manfred surname: Hallschmid fullname: Hallschmid, Manfred email: manfred.hallschmid@uni-tuebingen.de organization: 5Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM) (M.He., H.P., H.-U.H., A.F., M.Ha.), 72076 Tübingen, Germany |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24423295$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Adipose tissue Administration, Intranasal Adult Biopsy Blood Glucose - metabolism Body fat Central nervous system Fatty Acids, Nonesterified - blood Fatty Acids, Nonesterified - metabolism Female Glycerol Humans Insulin Insulin - administration & dosage JCEM Online: Brief Reports Lipid metabolism Lipolysis Lipolysis - drug effects Male Subcutaneous Fat - drug effects Subcutaneous Fat - metabolism Triglycerides |
| Title | Intranasal Insulin Suppresses Systemic but Not Subcutaneous Lipolysis in Healthy Humans |
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