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Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice

BACKGROUND & AIMS: 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 th...

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Autores principales: Duwaerts, Caroline C., Amin, Amin M., Siao, Kevin, Her, Chris, Fitch, Mark, Beysen, Carine, Turner, Scott M., Goodsell, Amanda, Baron, Jody L., Grenert, James P., Cho, Soo-Jin, Maher, Jacquelyn J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472193/
https://www.ncbi.nlm.nih.gov/pubmed/28649594
http://dx.doi.org/10.1016/j.jcmgh.2017.04.004
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author Duwaerts, Caroline C.
Amin, Amin M.
Siao, Kevin
Her, Chris
Fitch, Mark
Beysen, Carine
Turner, Scott M.
Goodsell, Amanda
Baron, Jody L.
Grenert, James P.
Cho, Soo-Jin
Maher, Jacquelyn J.
author_facet Duwaerts, Caroline C.
Amin, Amin M.
Siao, Kevin
Her, Chris
Fitch, Mark
Beysen, Carine
Turner, Scott M.
Goodsell, Amanda
Baron, Jody L.
Grenert, James P.
Cho, Soo-Jin
Maher, Jacquelyn J.
author_sort Duwaerts, Caroline C.
collection PubMed
description BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-54721932017-06-23 Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice Duwaerts, Caroline C. Amin, Amin M. Siao, Kevin Her, Chris Fitch, Mark Beysen, Carine Turner, Scott M. Goodsell, Amanda Baron, Jody L. Grenert, James P. Cho, Soo-Jin Maher, Jacquelyn J. Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Elsevier 2017-04-22 /pmc/articles/PMC5472193/ /pubmed/28649594 http://dx.doi.org/10.1016/j.jcmgh.2017.04.004 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Duwaerts, Caroline C.
Amin, Amin M.
Siao, Kevin
Her, Chris
Fitch, Mark
Beysen, Carine
Turner, Scott M.
Goodsell, Amanda
Baron, Jody L.
Grenert, James P.
Cho, Soo-Jin
Maher, Jacquelyn J.
Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title_full Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title_fullStr Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title_full_unstemmed Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title_short Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice
title_sort specific macronutrients exert unique influences on the adipose-liver axis to promote hepatic steatosis in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472193/
https://www.ncbi.nlm.nih.gov/pubmed/28649594
http://dx.doi.org/10.1016/j.jcmgh.2017.04.004
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