Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to
Promote Hepatic Steatosis in Mice.
Authors Duwaerts CC, Amin AM, Siao K, Her C, Fitch M, Beysen C, Turner SM, Goodsell A,
Baron JL, Grenert JP, Cho SJ, Maher JJ
Submitted By Submitted Externally on 9/13/2017
Status Published
Journal Cellular and molecular gastroenterology and hepatology
Year 2017
Date Published 9/1/2017
Volume : Pages 4 : 223 - 236
PubMed Reference 28649594
Abstract The factors that distinguish metabolically healthy obesity from metabolically
unhealthy obesity are not well understood. Diet has been implicated as a
determinant of the unhealthy obesity phenotype, but which aspects of the diet
induce dysmetabolism are unknown. The goal of this study was to investigate
whether specific macronutrients or macronutrient combinations provoke
dysmetabolism in the context of isocaloric, high-energy diets., Mice were fed 4
high-energy diets identical in calorie and nutrient content but different in
nutrient composition for 3 weeks to 6 months. The test diets contained 42%
carbohydrate (sucrose or starch) and 42% fat (oleate or palmitate). Weight and
glucose tolerance were monitored; blood and tissues were collected for
histology, gene expression, and immunophenotyping., Mice gained weight on all 4
test diets but differed significantly in other metabolic outcomes. Animals fed
the starch-oleate diet developed more severe hepatic steatosis than those on
other formulas. Stable isotope incorporation showed that the excess hepatic
steatosis in starch-oleate-fed mice derived from exaggerated adipose tissue
lipolysis. In these mice, adipose tissue lipolysis coincided with adipocyte
necrosis and inflammation. Notably, the liver and adipose tissue abnormalities
provoked by starch-oleate feeding were reproduced when mice were fed a
mixed-nutrient Western diet with 42% carbohydrate and 42% fat., The
macronutrient composition of the diet exerts a significant influence on
metabolic outcome, independent of calories and nutrient proportions.
Starch-oleate appears to cause hepatic steatosis by inducing progressive adipose
tissue injury. Starch-oleate phenocopies the effect of a Western diet;
consequently, it may provide clues to the mechanism whereby specific nutrients
cause metabolically unhealthy obesity.