Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

Abstract

Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

• Authors: Marc-André Laplante, Alexandre Charbonneau, Rita Kohen Avramoglu, Patricia Pelletier, Xiangping Fang, Hélène Bachelard, Seppo Ylä-Herttuala, Markku Laakso, Jean-Pierre Després, Yves Deshaies, Gary Sweeney, Patrick Mathieu, André Marette
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 305 Issue 5 Pg. E573-84 (Sep 01 2013) ISSN: 1522-1555 [Electronic] United States
• PMID: 23820620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, Dietary
• Triglycerides

Topics

• Animals
• Atherosclerosis (metabolism)
• Cholesterol, Dietary (administration & dosage, metabolism)
• Diabetes Mellitus, Experimental (metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Disease Models, Animal
• Glucose Clamp Technique
• Glucose Tolerance Test
• Histocytochemistry
• Insulin Resistance
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle Contraction (physiology)
• Specific Pathogen-Free Organisms
• Triglycerides (administration & dosage, metabolism)