TITLE

Intranasal application of the melanocortin 4 receptor agonist MSH/ACTH(4-10) in humans causes lipolysis in white adipose tissue

AUTHOR(S)
Wellhöner, P; Hörster, R; Jacobs, F; Sayk, F; Lehnert, H; Dodt, C
PUB. DATE
May 2012
SOURCE
International Journal of Obesity;May2012, Vol. 36 Issue 5, p703
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Objective:The melanocortin system has a highly significant role in the hypothalamic regulation of body weight and energy expenditure. In animals, intracerebroventricular infusion of melanocortin receptor 4 (MCR-4) agonists increases basal metabolic rate through activation of the sympathetic nervous system and subsequently reduces food intake. In humans, direct access of MCR-4 agonists to the central nervous system can be achieved by a transnasal route, which leads to weight loss with chronic administration. In the present study, we aimed at investigating the effects of intranasally administered MC4-R agonist MSH/ACTH(4-10) on lipolysis and sympathetic nervous system activity in healthy humans.Design:Healthy normal weight, male volunteers (n=10) received either 10 mg MSH/ACTH(4-10) or placebo intranasally in a double-blinded randomized crossover design. Interstitial glycerol release was assessed by microdialysis in abdominal white adipose tissue (WAT) and in skeletal muscle (SM) of the forearm. Local blood flow, systemic blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) within the superficial peroneal nerve were recorded at rest and after nitroprusside infusion.Results:At 45 min after MSH/ACTH(4-10) administration WAT glycerol concentrations increased by 53.4±19.3% compared with baseline conditions (P<0.05) and remained significantly higher throughout the experiment when compared with placebo (P<0.05) while local glycerol release in SM was not significantly affected. Resting MSNA was not altered by MSH/ACTH(4-10) administration; however, sympathoexcitation by intravenous nitroprusside was markedly elevated (MSH/ACTH(4-10) 569±69% increase to baseline; placebo: 315±64%; P<0.01).Conclusion:Intranasally administered MCR-4 agonist MSH/ACTH 4-10 increases both subcutaneous WAT lipolysis and MSNA, which suggests a direct central nervous peptide effect in humans on key factors of human energy metabolism.
ACCESSION #
75008835

 

Related Articles

  • Recruited brown adipose tissue as an antiobesity agent in humans. Yoneshiro, Takeshi; Aita, Sayuri; Matsushita, Mami; Kayahara, Takashi; Kameya, Toshimitsu; Kawai, Yuko; Iwanaga, Toshihiko; Saito, Masayuki // Journal of Clinical Investigation;Aug2013, Vol. 123 Issue 8, p3404 

    Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related...

  • Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight.  // American Journal of Clinical Nutrition;Oct2008, Vol. 88 Issue 4, p906 

    The article presents a study of whether the disproportionate reduction in energy expenditure persists in persons who have maintained a reduced body weight. The study used indirect calorimetry to measure the resting energy expenditure (REE) and the thermic effect of feeding (TEF). Results showed...

  • The Fate of Fat: A Response. Saely, Christoph H.; Drexel, Veronika; Drexel, Heinz // Gerontology;2012, Vol. 58 Issue 2, p123 

    Brown adipose tissue (BAT) activity increases energy expenditure and therefore may facilitate weight loss. The principal physiological trigger for its activation is stimulation of the sympathetic nervous system by decreased ambient temperature. Also, direct pharmacological stimulation of the...

  • Development and Verification of a Mouse Model for Roux-en-Y Gastric Bypass Surgery with a Small Gastric Pouch. Zheng Hao; Zhiyun Zhao; Berthoud, Hans-Rudolf; Jianping Ye // PLoS ONE;Jan2013, Vol. 8 Issue 1, Special section p1 

    Existing mouse models of Roux-en-Y gastric bypass (RYGB) surgery are not comparable to human RYGB in gastric pouch volume for a large or absent gastric volume. The aim of this study was to develop and characterize a mouse RYGB model that closely replicates gastric pouch size of human RYGB...

  • The Physiology of Body Weight Regulation: Are We Too Efficient for Our Own Good? Dokken, Betsy B.; Tsao, Tsu-Shuen // Diabetes Spectrum;Summer2007, Vol. 20 Issue 3, p166 

    Understanding the physiology behind the regulation of body weight can help clinicians treat and educate obese patients. This article reviews the current knowledge of body weight regulation and the metabolic changes that occur in the body in response to weight loss. The physiological basis for...

  • The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis. Koponen, Taina; Cerrada-Gimenez, Marc; Pirinen, Eija; Hohtola, Esa; Paananen, Jussi; Vuohelainen, Susanna; Tusa, Maija; Pirnes-Karhu, Sini; Heikkinen, Sami; Virkamäki, Antti; Uimari, Anne; Alhonen, Leena; Laakso, Markku // Amino Acids;Feb2012, Vol. 42 Issue 2/3, p427 

    The mitochondrial biogenesis and energy expenditure regulator, PGC-1α, has been previously reported to be induced in the white adipose tissue (WAT) and liver of mice overexpressing spermidine/spermine N-acetyltransferase (SSAT). The activation of PGC-1α in these mouse lines leads to...

  • Innate Obesity, Revealed by Selection Markers, Confers Significant Imprint of Hypothalamic Genes Controlling Energy Expenditure. Henry, Belinda A. // Neuroendocrinology;Apr2017, Vol. 104 Issue 4, p319 

    The incidence of obesity is rapidly escalating and has reached epidemic proportions. In all species, including rodents, humans, and sheep, there is large variation in the degree of weight gain across individuals in response to an obesogenic environment. This individual variation is, at least in...

  • TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator. Tsai, Vicky Wang-Wei; Macia, Laurence; Johnen, Heiko; Kuffner, Tamara; Manadhar, Rakesh; Jørgensen, Sebastian Beck; Lee-Ng, Ka Ki Michelle; Zhang, Hong Ping; Wu, Liyun; Marquis, Christopher Peter; Jiang, Lele; Husaini, Yasmin; Lin, Shu; Herzog, Herbert; Brown, David A.; Sainsbury, Amanda; Breit, Samuel N. // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite,...

  • Estimation of Activity Related Energy Expenditure and Resting Metabolic Rate in Freely Moving Mice from Indirect Calorimetry Data. Van Klinken, Jan Bert; van den Berg, Sjoerd A. A.; Havekes, Louis M.; Van^Dijk, Ko Willems // PLoS ONE;May2012, Vol. 7 Issue 5, p1 

    Physical activity (PA) is a main determinant of total energy expenditure (TEE) and has been suggested to play a key role in body weight regulation. However, thus far it has been challenging to determine what part of the expended energy is due to activity in freely moving subjects. We developed a...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics