Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state.
Increases in ventromedial hypothalamic (VMH) norepinephrine (NE) levels and/or activities have been observed in a variety of animal models of the obese insulin-resistant condition. This study examined the metabolic effects of chronic NE infusion (25 nmol/h) into the unilateral VMH of normal rats. Within 4 days, VMH NE infusion significantly increased plasma insulin (140%), glucagon (45%), leptin (300%), triglyceride (100%), abdominal fat pad weight (50%), and white adipocyte lipogenic (100%) and lipolytic (100%) activities relative to vehicle-infused rats. Furthermore, isolated islet insulin secretory response to glucose (15 mM) within 4 days of such treatment was increased over twofold (P < 0.05). Among treated animals, fat stores continued to increase over time and plateaued at approximately 2 wk (3-fold increase), remaining elevated to the end of the study (5 wk). By week 4 of treatment, NE infusion induced glucose intolerance as evidenced by a 32% increase in plasma glucose total area under the glucose tolerance test curve (P < 0.01). Whole body fat oxidation rate measured after 5 wk of infusion was significantly increased among treated animals as evidenced by a reduced respiratory quotient (0.87 +/- 0.01) relative to controls (0. 90 +/- 0.01). VMH NE infusion induced hyperphagia (30%) only during the first week and did not affect body weight over the 5-wk period. Increases in VMH NE activity that are common among obese insulin-resistant animal models can cause the development of this obese glucose-intolerant (metabolic) syndrome.
Cincotta
A H
AH
Ergo Science Corporation, North Andover, Massachusetts 01845, USA. ahcincotta@aol.com
Luo
S
S
Zhang
Y
Y
Liang
Y
Y
Bina
K G
KG
Jetton
T L
TL
Scislowski
P W
PW
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D050260:Carbohydrate Metabolism; D004702:Endocrine Glands / Q000503:physiopathology; D005260:Female; D018149:Glucose Intolerance; D006728:Hormones / Q000097:blood; D007267:Injections; D007545:Isoproterenol / Q000494:pharmacology; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage* / Q000494:pharmacology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013577:Syndrome; D013997:Time Factors; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
D006728:Hormones; D020738:Leptin; D007545:Isoproterenol; D009638:Norepinephrine