<i>MEK6</i> Overexpression Exacerbates Fat Accumulation and Inflammatory Cytokines in High-Fat Diet-Induced Obesity
Obesity is a state of abnormal fat accumulation caused by an energy imbalance potentially caused by changes in multiple factors. <i>MEK6</i> engages in cell growth, such as inflammation and apoptosis, as one of the MAPK signaling pathways. The <i>MEK6</i> gene was found to be...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/24/13559 |
| Summary: | Obesity is a state of abnormal fat accumulation caused by an energy imbalance potentially caused by changes in multiple factors. <i>MEK6</i> engages in cell growth, such as inflammation and apoptosis, as one of the MAPK signaling pathways. The <i>MEK6</i> gene was found to be related to <i>RMR</i>, a gene associated with obesity. Because only a few studies have investigated the correlation between <i>MEK6</i> and obesity or the relevant mechanisms, we conducted an experiment using a Tg<i><sup>MEK6</sup></i> model with <i>MEK6</i> overexpression with non-Tg and chow diet as the control to determine changes in lipid metabolism in plasma, liver, and adipose tissue after a 15-week high-fat diet (HFD). <i>MEK6</i> overexpression in the Tg<i><sup>MEK6</sup></i> model significantly increased body weight and plasma triglyceride and total cholesterol levels. p38 activity declined in the liver and adipose tissues and lowered lipolysis, oxidation, and thermogenesis levels, contributing to decreased energy consumption. In the liver, lipid formation and accumulation increased, and in adipose, adipogenesis and hypertrophy increased. The adiponectin/leptin ratio significantly declined in plasma and adipose tissue of the Tg<i><sup>MEK6</sup></i> group following <i>MEK6</i> expression and the HFD, indicating the role of <i>MEK6</i> expression in adipokine regulation. Plasma and bone-marrow-derived macrophages (BMDM) of the Tg<i><sup>MEK6</sup></i> group increased <i>MEK6</i> expression-dependent secretion of pro-inflammatory cytokines but decreased levels of anti-inflammatory cytokines, further exacerbating the results exhibited by the diet-induced obesity group. In conclusion, this study demonstrated the synergistic effect of <i>MEK6</i> with HFD in fat accumulation by significantly inhibiting the mechanisms of lipolysis in the adipose and M2 associated cytokines secretion in the BMDM. |
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| ISSN: | 1661-6596 1422-0067 |