Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice
Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic action...
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MDPI AG
2021-10-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/43/3/128 |
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| author | Hsuan-Miao Liu Cheng-Hui Wang Zi-Yu Chang Tse-Hung Huang Tzung-Yan Lee |
| author_facet | Hsuan-Miao Liu Cheng-Hui Wang Zi-Yu Chang Tse-Hung Huang Tzung-Yan Lee |
| author_sort | Hsuan-Miao Liu |
| collection | DOAJ |
| description | Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFβR2 levels. In white adipose tissue, a set of lipogenesis-related genes, <i>Srebp1</i>, <i>Fas</i>, and <i>Scd-1</i> were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of <i>Tfam</i>, <i>Cd137</i>, <i>Tmem26</i>, <i>Ucp1</i> expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways. |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-4e63d177a3154247ae19b8a42c2c14612023-11-23T07:44:03ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-10-014331828184310.3390/cimb43030128Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> MiceHsuan-Miao Liu0Cheng-Hui Wang1Zi-Yu Chang2Tse-Hung Huang3Tzung-Yan Lee4Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333, TaiwanInstitute of Traditional Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung City 204, TaiwanGraduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, TaiwanInsulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFβR2 levels. In white adipose tissue, a set of lipogenesis-related genes, <i>Srebp1</i>, <i>Fas</i>, and <i>Scd-1</i> were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of <i>Tfam</i>, <i>Cd137</i>, <i>Tmem26</i>, <i>Ucp1</i> expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways.https://www.mdpi.com/1467-3045/43/3/128losartaninsulin resistanceobesitymacrophage polarizationmitochondrial functionwhite adipose browning |
| spellingShingle | Hsuan-Miao Liu Cheng-Hui Wang Zi-Yu Chang Tse-Hung Huang Tzung-Yan Lee Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice Current Issues in Molecular Biology losartan insulin resistance obesity macrophage polarization mitochondrial function white adipose browning |
| title | Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice |
| title_full | Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice |
| title_fullStr | Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice |
| title_full_unstemmed | Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice |
| title_short | Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in <i>ob</i><i>/ob</i> Mice |
| title_sort | losartan attenuates insulin resistance and regulates browning phenomenon of white adipose tissue in i ob i i ob i mice |
| topic | losartan insulin resistance obesity macrophage polarization mitochondrial function white adipose browning |
| url | https://www.mdpi.com/1467-3045/43/3/128 |
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