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Joibari, Masoumeh Motamedi
Publications (2 of 2) Show all publications
Heverin, M., Ali, Z., Olin, M., Tillander, V., Joibari, M. M., Makoveichuk, E., . . . Björkhem, I. (2017). On the regulatory importance of 27-hydroxycholesterol in mouse liver. Journal of Steroid Biochemistry and Molecular Biology, 169, 10-21
Open this publication in new window or tab >>On the regulatory importance of 27-hydroxycholesterol in mouse liver
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2017 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 169, p. 10-21Article, review/survey (Refereed) Published
Abstract [en]

27-Hydroxycholesterol (27OH) is a strong suppressor of cholesterol synthesis and a weak activator of LXR in vitro. The regulatory importance of 27OH in vivo is controversial. Here we utilized male mice with increased levels of 27OH either due to increased production (CYP27A1 transgenic mice) or reduced metabolism (Cyp7b1-/- mice). We also used mice lacking 27OH due to a knockout of Cyp27a1. The latter mice were treated with cholic acid to compensate for reduced bile acid synthesis. The effects of the different levels of 27OH on Srebp- and other LXR-regulated genes in the liver were investigated. In the liver of CYP27tg mice we found a modest increase of the mRNA levels corresponding to the LXR target genes Cyp7b1 and Abca1. A number of other LXR-regulated genes were not affected. The effect on Abca1 mRNA was not seen in the liver of Cyp7b1-/- mice. There were little or no effects on cholesterol synthesis. In the liver of the Cyp27-/- mice treated with 0.025% cholic acid there was no significant effect of the knockout on the LXR target genes. In a previous work triple-knockout mice deficient in the biosynthesis of 24S-hydroxycholesterol, 25-hydroxycholesterol and 27OH were shown to have impaired response to dietary cholesterol, suggesting side-chain oxidized oxysterols to be mediators in cholesterol-induced effects on LXR target genes at a transcriptional level (Chen W. et al., Cell Metab. 5 (2007) 73-79). The hydroxylated oxysterol responsible for the effect was not defined. We show here that treatment of wildtype mice with dietary cholesterol under the same conditions as in the above study induced the LXR target genes Lpl, Abcg8 and Srebp1c in wild type mice but failed to activate the same genes in mice lacking 27-hydroxycholesterol due to a knockout of Cyp27. We failed to demonstrate the above effects at the protein level (Abcg8) or at the activity level (Lpl). The results suggest that 27OH is not an important regulator of Srebp- or LXR regulated genes under basal conditions in mouse liver. On the other hand 27OH appears to mediate cholesterol-induced effects on some LXR target genes at a transcriptional level under some in vivo conditions. 

Place, publisher, year, edition, pages
Elsevier, 2017
Cholesterol metabolism, Gene expression, Nuclear receptor, OXysterols, Cytochrome P-450, Cyp27-/- mice, Lipoprotein lipase, Abcg8, Srebp1c, Lxr
National Category
Cell and Molecular Biology
urn:nbn:se:umu:diva-136070 (URN)10.1016/j.jsbmb.2016.02.001 (DOI)000401391300003 ()26851362 (PubMedID)2-s2.0-84959419016 (Scopus ID)

Special Issue: SI

Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2023-03-24Bibliographically approved
Nilsson, J., Ericsson, M., Joibari, M. M., Anderson, F., Carlsson, L., Nilsson, S. K., . . . Burén, J. (2016). A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function in pair-fed female C57BL/6J mice. Nutrition & Metabolism, 13, Article ID 79.
Open this publication in new window or tab >>A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function in pair-fed female C57BL/6J mice
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2016 (English)In: Nutrition & Metabolism, E-ISSN 1743-7075, Vol. 13, article id 79Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Excess body fat is a major health issue and a risk factor for the development of numerous chronic diseases. Low-carbohydrate diets like the Atkins Diet are popular for rapid weight loss, but the long-term consequences remain the subject of debate. The Scandinavian low-carbohydrate high-fat (LCHF) diet, which has been popular in Scandinavian countries for about a decade, has very low carbohydrate content (~5 E %) but is rich in fat and includes a high proportion of saturated fatty acids. Here we investigated the metabolic and physiological consequences of a diet with a macronutrient composition similar to the Scandinavian LCHF diet and its effects on the organs, tissues, and metabolism of weight stable mice.

METHODS: Female C57BL/6J mice were iso-energetically pair-fed for 4 weeks with standard chow or a LCHF diet. We measured body composition using echo MRI and the aerobic capacity before and after 2 and 4 weeks on diet. Cardiac function was assessed by echocardiography before and after 4 weeks on diet. The metabolic rate was measured by indirect calorimetry the fourth week of the diet. Mice were sacrificed after 4 weeks and the organ weight, triglyceride levels, and blood chemistry were analyzed, and the expression of key ketogenic, metabolic, hormonal, and inflammation genes were measured in the heart, liver, and adipose tissue depots of the mice using real-time PCR.

RESULTS: The increase in body weight of mice fed a LCHF diet was similar to that in controls. However, while control mice maintained their body composition throughout the study, LCHF mice gained fat mass at the expense of lean mass after 2 weeks. The LCHF diet increased cardiac triglyceride content, impaired cardiac function, and reduced aerobic capacity. It also induced pronounced alterations in gene expression and substrate metabolism, indicating a unique metabolic state.

CONCLUSIONS: Pair-fed mice eating LCHF increased their percentage of body fat at the expense of lean mass already after 2 weeks, and after 4 weeks the function of the heart deteriorated. These findings highlight the urgent need to investigate the effects of a LCHF diet on health parameters in humans.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2016
Low-carbohydrate diet, Heart, Mouse
National Category
Clinical Medicine Physiology Nutrition and Dietetics Cardiac and Cardiovascular Systems
urn:nbn:se:umu:diva-128938 (URN)10.1186/s12986-016-0132-8 (DOI)000388140200001 ()27891164 (PubMedID)2-s2.0-84995511496 (Scopus ID)
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2024-03-06Bibliographically approved

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