Vaccination against Weight Gain

• Autor: Zorrilla, Eric P. ; Iwasaki, Shinichi ; Moss, Jason A. ; Chang, Jason ; Otsuji, Jonathan ; Inoue, Koki ; Meijler, Michael M. ; Janda, Kim D.
• Assuntos: Amino Acid Sequence ; Animals ; Antibodies ; Antibodies - blood ; Biological Sciences ; Body Composition - immunology ; Body weight ; Energy Metabolism - immunology ; Feed conversion ratio ; Feeding Behavior - physiology ; Food intake ; Ghrelin ; Haptens ; Haptens - immunology ; Homeostasis - immunology ; Immunization ; Inflammation - immunology ; Male ; Molecular Sequence Data ; Obesity ; Obesity - immunology ; Obesity - prevention & control ; Peptide Hormones - antagonists & inhibitors ; Peptide Hormones - blood ; Peptide Hormones - chemistry ; Peptide Hormones - immunology ; Rats ; Rats, Wistar ; Rodents ; Thinness - immunology ; Vaccination ; Vaccines ; Vaccines - immunology ; Vaccines - pharmacology ; Vaccines, Subunit - blood ; Vaccines, Subunit - immunology ; Weight control ; Weight gain ; Weight Gain - physiology
• É parte de: Proceedings of the National Academy of Sciences - PNAS, 2006-08, Vol.103 (35), p.13226-13231
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  Present address: Department of Neuropsychiatry, Osaka City University, 1-4-3 Asahi machi, Abeno-ku, Osaka City, Osaka 545-8585, Japan.
  Communicated by Richard A. Lerner, The Scripps Research Institute, La Jolla, CA, June 29, 2006
  Author contributions: E.P.Z., J.A.M., M.M.M., and K.D.J. designed research; E.P.Z., S.I., J.A.M., J.C., J.O., and M.M.M. performed research; J.A.M., M.M.M., and K.D.J. contributed new reagents/analytic tools; E.P.Z., S.I., J.C., J.O., K.I., and M.M.M. analyzed data; and E.P.Z., S.I., K.I., M.M.M., and K.D.J. wrote the paper.
  
• Descrição: Obesity endangers the lives of millions of people worldwide, through comorbidities such as heart disease, cancers, type 2 diabetes, stroke, arthritis, and major depression. New approaches to control body weight remain a high priority. Vaccines traditionally have been used to protect against infectious diseases and, more recently, for unconventional targets such as drug addiction. Methodologies that could specifically modulate the bioavailability of an endogenous molecule that regulates energy balance might provide a new foundation for treating obesity. Here we show that active vaccination of mature rats with ghrelin immunoconjugates decreases feed efficiency, relative adiposity, and body weight gain in relation to the immune response elicited against ghrelin in its active, acylated form. Three active vaccines based on the 28-aa residue sequence of ghrelin, a gastric endocrine hormone, were used to immunize adult male Wistar rats (n = 17). Synthetic ghrelin analogs were prepared that spanned residues 1-10 [ghrelin (1-10) Ser-3(butanoyl) hapten, Ghr1], 13-28 [ghrelin (13-28) hapten, Ghr2], and 1-28 [ghrelin(1-28) Ser-3(butanoyl) hapten, Ghr3], and included n-butanoyl esters at Ser-3. Groups immunized with Ghr1 or Ghr3 showed greater and more selective plasma binding capacity for the active, Ser-3-(n-octanoyl) form of ghrelin as compared with Ghr2 or keyhole limpet hemocyanin vaccinated controls. Accordingly, they gained less body weight, with sparing of lean mass and preferential reduction of body fat, consistent with reduced circulating leptin levels. The ratio of brain/serum ghrelin levels was lower in rats with strong anti-ghrelin immune responses. Effects were not attributable to nonspecific inflammatory responses. Vaccination against the endogenous hormone ghrelin can slow weight gain in rats by decreasing feed efficiency.
  
• Editor: United States: National Academy of Sciences
  
• Idioma: Inglês