Peripheral, but not central, administration of adiponectin reduces visceral adiposity and upregulates the expression of uncoupling protein in agouti yellow (Ay/a) obese mice

Diabetes. 2003 Sep;52(9):2266-73. doi: 10.2337/diabetes.52.9.2266.

Abstract

To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow (A(y)/a) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A(y)/a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A(y)/a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos-like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0-15 micro g/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin
  • Adipose Tissue, Brown / drug effects*
  • Animals
  • Blood Glucose / drug effects
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Carrier Proteins / genetics*
  • Eating / drug effects
  • Gene Expression / drug effects
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Insulin / blood
  • Intercellular Signaling Peptides and Proteins*
  • Ion Channels
  • Liver / drug effects
  • Male
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Obese
  • Mitochondrial Proteins*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology
  • Obesity / drug therapy*
  • Obesity / physiopathology
  • Proteins / genetics
  • Proteins / pharmacology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / analysis
  • Triglycerides / blood
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Up-Regulation / drug effects
  • Viscera

Substances

  • Adiponectin
  • Blood Glucose
  • Carrier Proteins
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Ion Channels
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Triglycerides
  • Ucp1 protein, mouse
  • Ucp2 protein, mouse
  • Uncoupling Protein 1
  • Uncoupling Protein 2