Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice
LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-a...
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MDPI AG
2022-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/21/4503 |
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| author | Chuanxing Feng Yuge Jiang Shiying Li Yueting Ge Yonghui Shi Xue Tang Guowei Le |
| author_facet | Chuanxing Feng Yuge Jiang Shiying Li Yueting Ge Yonghui Shi Xue Tang Guowei Le |
| author_sort | Chuanxing Feng |
| collection | DOAJ |
| description | LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H<sub>2</sub>O<sub>2</sub> in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H<sub>2</sub>O<sub>2</sub>-induced injury and apoptosis by inhibiting H19. |
| first_indexed | 2024-03-09T18:45:40Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T18:45:40Z |
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| series | Nutrients |
| spelling | doaj.art-0b0b302bf2f54d058ffbba331b5513e22023-11-24T06:12:33ZengMDPI AGNutrients2072-66432022-10-011421450310.3390/nu14214503Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant MiceChuanxing Feng0Yuge Jiang1Shiying Li2Yueting Ge3Yonghui Shi4Xue Tang5Guowei Le6State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaCenter for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaLncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H<sub>2</sub>O<sub>2</sub> in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H<sub>2</sub>O<sub>2</sub>-induced injury and apoptosis by inhibiting H19.https://www.mdpi.com/2072-6643/14/21/4503methionine restrictionneuron apoptosiscognitive abilityinsulin resistanceoxidative stress |
| spellingShingle | Chuanxing Feng Yuge Jiang Shiying Li Yueting Ge Yonghui Shi Xue Tang Guowei Le Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice Nutrients methionine restriction neuron apoptosis cognitive ability insulin resistance oxidative stress |
| title | Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice |
| title_full | Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice |
| title_fullStr | Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice |
| title_full_unstemmed | Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice |
| title_short | Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice |
| title_sort | methionine restriction improves cognitive ability by alleviating hippocampal neuronal apoptosis through h19 in middle aged insulin resistant mice |
| topic | methionine restriction neuron apoptosis cognitive ability insulin resistance oxidative stress |
| url | https://www.mdpi.com/2072-6643/14/21/4503 |
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