chronic north american ginseng administration alters metabolic variables in the rat megan migchels...
TRANSCRIPT
Chronic North American Ginseng Administration Alters Metabolic
Variables in the Rat
Megan Migchels Supervisor: Dr. J. Ciriello2011/01/24
Overview
Background• Obesity • Obstructive Sleep Apnea• Ginseng
Hypothesis Model Preliminary Data Future experiments Questions
The Obesity Epidemic
• ~ 61% of Canadians are overweight
• This increases the risk of • Cardiovascular disease• Hypertension• Cancer• Diabetes
• Arguably leading cause of preventable death
Leptin
Secreted by adipocytes into the
bloodstream Acts on receptors in the hypothalamus
• Signals satiety• Increases energy expenditure through sympathetic activation
Initially thought to be an adipocyte signal that
functioned to prevent obesity• Leptin deficiency results in obesity• Leptin resistance in obesity
• ** Considered to play an important role in the development of hypertension in obesity**
Sleep Apnea (Intermittent Hypoxia)
Sleep Apnea is a serious disorder that occurs when a person's breathing is interrupted (stopped) during sleep.
Apnea is Greek for “without breath”. People with untreated sleep apnea stop breathing
repeatedly during their sleep, sometimes hundreds of times.
Holding your breath leads to decreased blood oxygen levels (hypoxia), which has serious consequences on the body.
Obstructive Sleep Apnea (OSA) • OSA- intermittent, cyclical cessations or
reductions of airflow because of an obstructed airway
• Prevalence of OSA is expected to rise in the coming years in response to the current obesity epidemic
Metabolic Syndrome
Ginseng
Ginseng has been used for centuries as a medicinal herb to replenish energy, reduce susceptibility to illness and promote health
Panax ginseng- Asian ginseng Panax quinquefolius- North American ginseng
Most researched herb in the world• Approximately 5% of the population of
Western countries consume ginseng
• Ginsenosides- active ingredient • The two types of ginseng differ in chemical
composition and have specific biological effects
• Previous studies: Asian Ginseng• Suggested to have anti-obesity effects, to decrease
plasma triglyceride and leptin levels (Lee, 2010)• Suggested to be anti-hypertensive (Yanai, 2006)• Improves the metabolic syndrome (Yun, 2007)
• However, little is known about the effects of
North American ginseng on cardiovascular
disease and obesity
• North American Ginseng contains 3-5x greater ginsenoside content than Asian Ginseng.
• North American Ginseng contains greater levels of ginsenoside Rb1, a phytoestrogen which has been seen to have hypotensive effects.
• North American Ginseng contains greater levels of ginsenoside Re which has vasodilatory and antihyperlipidemic properties.
Obstructive Sleep ApneaSympathetic ActivityRenin-AngiotensinOxidative Stress
Insulin ResistanceHypoxemia
Vascular Inflammation
ObesityInsulin Resistance
Vascular InflammationOxidative Stress
Endothelial DysfunctionSympathetic ActivityRenin-Angiotensin
Obstructive Sleep Apnea Increases the Risk of Cardiovascular Disease
Mechanical Obstruction of Airway
Risk Factors
Dr. John Ciriello, BSc, MSc, PhDProfessor of Physiology, Pharmacology and NeuroscienceSchulich School of Medicine and DentistryUniversity of Western Ontario – 2009.
Cardiovascular Disease(Risk Factors)Hypertension
StrokeIschemic Heart DiseaseCardiac Arrhythmias
Atherosclerosis
Patients with essential hypertension exhibit augmented increases in sympathetic nerve activity to hypoxia
Obese patients exhibit augmented increases in sympathetic nerve activityGinseng? Ginseng?
Ginseng?
Cardiovascular disease is a growing concern in our society • Hypertension• Obesity• Obstructive Sleep Apnea
Rationale
Overall Objective: • Investigate the effects of NAG treatment on the
metabolic and arterial pressure effects induced by chronic intermittent hypoxia (CIH) in normal and obese rats.
Hypothesis 1 (current ongoing study):
Chronic ingestion of NAG will reduce circulating levels of leptin• This reduction in leptin will ameliorate the effects of
obesity and CIH on the development of hypertension, dislipidemia, and insulin resistance in the obese rat.
Sprague Dawley normotensive rats on a standard rat chow diet
Sprague Dawley rats on a high-fat diet (45kcal fat)
Normal and obese Sprague Dawley rats exposed to Chronic Intermittent Hypoxia (60s episode at 6-7% O2 followed by 2 mins room air 20.5% O2.)
Ethanol extract of Panax quinquefolius by gavage: 0 or 250mg/kg
in 0.9%saline every day before 1900 hrs
for 28 days
Model
Weekly measurements of• Blood pressure and heart rate by indirect tail cuff
method (CODA system)• Body weight• Metabolism: Food/water intake, Urinary
output, Urine Na+, K+
After sacrifice• Brainstem effects: Fos/Fra to detect central areas
activated in response to administration of ginseng• Circulating levels of leptin, insulin• Obesity study:
Lipid profileso Triglycerideso Cholesterol
Retroperitoneal fat pad Epididymal fat pad
Cumulative Weight Change
0 1 2 3 40
50
100
150
200
ND Control ND GinsengHFD ControlHFD Ginseng
Week
Cu
mu
lati
ve
Weig
ht
Gain
(g
)
*
**
0 1 2 3 4275
325
375
425
475
525
575
ND ControlND GinsengHF ControlHF Ginseng
Week
Bod
y W
eig
ht
(g)
*
(n= 5)
(n= 5)(n= 5)
(n= 5)
Food Intake
(n= 4-5)(n= 4-5)
* * * ** * * *
Retroperitoneal Fat Pad*
*
**
Epididymal Fat Pad*
*
*
*
Plasma Leptin Concentration
*
*
*
*
*
*
Plasma Triglycerides
Total plasma cholesterol
Blood Glucose
Diet
**
Plasma Insulin
Insulin Resistance
Mean Arterial Pressure
Normal Diet
Normal Diet
High Fat Diet
Heart RateNormal Diet
High Fat Diet
Normal Diet
No statistical differences were seen in• Heart weight• Kidney weight• Hematocrit• Water intake• Urine output
Ongoing Studies
Increasing ‘n’ values• Normal/High fat diets
Analyze brain sections processed for cfos/Fra immunohistochemistry
Western blot and qPCR for long form of leptin receptor in brainstem/hypothalamus
Chronic Intermittent Hypoxia• Model of Obstructive Sleep Apnea
Questions