Dataset Information

Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR^-/- mice fed on high-fat diet.

ABSTRACT: Lipodystrophy is a severe adipose dysfunction that can be classified as congenital or acquired lipodystrophy, in term of the etiology. Previous knowledge about the metabolic disorders and cardiovascular consequences were mostly obtained from lipodystrophic mice with genetic defects. To completely rule out the genetic influence, we established a mouse model of acquired generalized lipodystrophy by surgical removal of multiple fat depots, including subcutaneous fat in the inguinal, visceral fat in the epididymis and brown fat in the scapula, in atherosclerosis-prone LDLR^-/- mice which were fed with a high-fat diet (HFD). It was observed that fat removal increased diet-induced hyperlipidemia, especially hypercholesteremia, as early as 2 weeks after HFD and till the end of HFD feeding. After 12 weeks on the HFD, the residual fats of fat-removed mice were found expanded. Although fat removal aggravated diet-induced lipid deposition in the liver and systemic insulin resistance, there was no significant difference in atherogenesis in fat-removed mice compared with sham-operated control mice. Acquired generalized lipodystrophy by surgical fat removal promoted metabolic disorders but not atherogenesis in LDLR^-/- mice fed on HFD.

SUBMITTER: Liu L

PROVIDER: S-EPMC6883051 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR<sup>-/-</sup> mice fed on high-fat diet.

Liu Lin L Liang Chenxi C Wang Xiaowei X Ding Xiayu X Lu Yingjing Y Dong Jinghui J Han Mei M Yang Hongyuan H Gao Mingming M Liao Jiawei J

Scientific reports 20191128 1

Lipodystrophy is a severe adipose dysfunction that can be classified as congenital or acquired lipodystrophy, in term of the etiology. Previous knowledge about the metabolic disorders and cardiovascular consequences were mostly obtained from lipodystrophic mice with genetic defects. To completely rule out the genetic influence, we established a mouse model of acquired generalized lipodystrophy by surgical removal of multiple fat depots, including subcutaneous fat in the inguinal, visceral fat in ...[more]

PMID: 31780791

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Project description:BackgroundToll-like receptor-2 (TLR2) promotes vascular smooth muscle cell (VSMC) transdifferentiation to chondrocytes and calcification in a p38 MAPK-dependent manner. Vascular 5-methoxytryptophan (5-MTP) is a newly identified factor with anti-inflammatory actions. As 5-MTP targets p38 MAPK for its actions, we postulated that 5-MTP protects against vascular chondrogenesis and calcification.MethodsHigh-fat diet-induced advanced atherosclerosis in mice were performed to investigate the effect of 5-MTP on atherosclerotic lesions and calcification. VSMCs were used to determine the role of 5-MTP in VSMC chondrogenic differentiation and calcification. Alizarin red S and Alcian blue staining were used to measure VSMC calcification and chondrogenic differentiation, respectively.Results5-MTP was detected in aortic tissues of ApoE-/- mice fed control chow. It was reduced in ApoE-/- mice fed high-fat diet (HFD), but was restored in ApoE-/-Tlr2-/- mice, suggesting that HFD reduces vascular 5-MTP production via TLR2. Intraperitoneal injection of 5-MTP or its analog into ApoE-/- mice fed HFD reduced aortic atherosclerotic lesions and calcification which was accompanied by reduction of chondrogenesis and calcium deposition. Pam3CSK4 (Pam3), ligand of TLR2, induced SMC phenotypic switch to chondrocytes. Pretreatment with 5-MTP preserved SMC contractile proteins and blocked Pam3-induced chondrocyte differentiation and calcification. 5-MTP inhibited HFD-induced p38 MAPK activation in vivo and Pam3-induced p38 MAPK activation in SMCs. 5-MTP suppressed HFD-induced CREB activation in aortic tissues and Pam3-induced CREB and NF-κB activation in SMCs.ConclusionsThese findings suggest that 5-MTP is a vascular arsenal against atherosclerosis and calcification by inhibiting TLR2-mediated SMC phenotypic switch to chondrocytes and the consequent calcification. 5-MTP exerts these effects by blocking p38 MAPK activation and inhibiting CREB and NF-κB transactivation activity.

Dataset Information

Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR-/- mice fed on high-fat diet.

Publications

Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR<sup>-/-</sup> mice fed on high-fat diet.

Similar Datasets

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Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR^-/- mice fed on high-fat diet.