A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice
The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are...
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MDPI AG
2021-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/10/3642 |
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| author | Ludivine Doridot Sarah A. Hannou Sarah A. Krawczyk Wenxin Tong Mi-Sung Kim Gregory S. McElroy Alan J. Fowler Inna I. Astapova Mark A. Herman |
| author_facet | Ludivine Doridot Sarah A. Hannou Sarah A. Krawczyk Wenxin Tong Mi-Sung Kim Gregory S. McElroy Alan J. Fowler Inna I. Astapova Mark A. Herman |
| author_sort | Ludivine Doridot |
| collection | DOAJ |
| description | The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease. |
| first_indexed | 2024-03-10T06:18:20Z |
| format | Article |
| id | doaj.art-92e8228cfcdd4b5280730b41525b6866 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T06:18:20Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-92e8228cfcdd4b5280730b41525b68662023-11-22T19:31:58ZengMDPI AGNutrients2072-66432021-10-011310364210.3390/nu13103642A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male MiceLudivine Doridot0Sarah A. Hannou1Sarah A. Krawczyk2Wenxin Tong3Mi-Sung Kim4Gregory S. McElroy5Alan J. Fowler6Inna I. Astapova7Mark A. Herman8Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADuke Molecular Physiology Institute, Duke University, Durham, NC 27701, USADivision of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADuke Molecular Physiology Institute, Duke University, Durham, NC 27701, USADivision of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADivision of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADivision of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADuke Molecular Physiology Institute, Duke University, Durham, NC 27701, USADuke Molecular Physiology Institute, Duke University, Durham, NC 27701, USAThe metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease.https://www.mdpi.com/2072-6643/13/10/3642fructosesteatosishypertriglyceridemiahyperinsulinemiaobesitytranscriptomics |
| spellingShingle | Ludivine Doridot Sarah A. Hannou Sarah A. Krawczyk Wenxin Tong Mi-Sung Kim Gregory S. McElroy Alan J. Fowler Inna I. Astapova Mark A. Herman A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice Nutrients fructose steatosis hypertriglyceridemia hyperinsulinemia obesity transcriptomics |
| title | A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice |
| title_full | A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice |
| title_fullStr | A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice |
| title_full_unstemmed | A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice |
| title_short | A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice |
| title_sort | systems approach dissociates fructose induced liver triglyceride from hypertriglyceridemia and hyperinsulinemia in male mice |
| topic | fructose steatosis hypertriglyceridemia hyperinsulinemia obesity transcriptomics |
| url | https://www.mdpi.com/2072-6643/13/10/3642 |
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