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Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice.

Abstract
Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.
AuthorsKatia De Angelis, Danielle D Senador, Cristiano Mostarda, Maria C Irigoyen, Mariana Morris
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 302 Issue 8 Pg. R950-7 (Apr 15 2012) ISSN: 1522-1490 [Electronic] United States
PMID22319048 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Insulin
  • Leptin
  • Lipids
  • Fructose
Topics
  • Animals
  • Baroreflex (drug effects, physiology)
  • Blood Glucose (metabolism)
  • Blood Pressure (drug effects, physiology)
  • Body Weight (drug effects, physiology)
  • Disease Models, Animal
  • Fructose (adverse effects)
  • Glucose Intolerance (chemically induced, metabolism, physiopathology)
  • Heart Rate (drug effects, physiology)
  • Insulin (blood)
  • Insulin Resistance (physiology)
  • Leptin (blood)
  • Lipids (blood)
  • Male
  • Mice
  • Sympathetic Nervous System (metabolism, physiopathology)

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