Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice.
OBJECTIVE
Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.


METHODS
Twelve-week-old mice were treated with stevioside (10 mg kg(-1), n=14) or placebo (n=20) for 12 weeks.


RESULTS
Stevioside had no effect on weight and triglycerides, but lowered glucose and insulin. Stevioside treatment improved adipose tissue maturation, and increased glucose transport, insulin signaling and antioxidant defense in white visceral adipose tissues. Together, these increases were associated with a twofold increase of adiponectin. In addition, stevioside reduced plaque volume in the aortic arch by decreasing the macrophage, lipid and oxidized low-density lipoprotein (ox-LDL) content of the plaque. The higher smooth muscle cell-to-macrophage ratio was indicative for a more stable plaque phenotype. The decrease in ox-LDL in the plaque was likely due to an increase in the antioxidant defense in the vascular wall, as evidenced by increased Sod1, Sod2 and Sod3. Circulating adiponectin was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the aorta of stevioside-treated mice.


CONCLUSIONS
Stevioside treatment was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the vascular wall, leading to inhibition of atherosclerotic plaque development and inducing plaque stabilization.
Geeraert
B
B
Atherosclerosis and Metabolism Unit, Department of Cardiovascular Diseases and Leuven Food Science and Nutrition Research Centre, Katholieke Universiteit Leuven, Leuven, Belgium.
Crombé
F
F
Hulsmans
M
M
Benhabilès
N
N
Geuns
J M
JM
Holvoet
P
P
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013549:Sweetening Agents / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D000975:Antioxidants; D001786:Blood Glucose; D045786:Diterpenes, Kaurane; D005960:Glucosides; D007328:Insulin; D013549:Sweetening Agents; D014280:Triglycerides; C012043:stevioside