Abstract
Obesity is a state of abnormal fat accumulation caused by an energy imbalance potentially caused by changes in multiple factors. MEK6 engages in cell growth, such as inflammation and apoptosis, as one of the MAPK signaling pathways. The MEK6 gene was found to be related to RMR, a gene associated with obesity. Because only a few studies have investigated the correlation between MEK6 and obesity or the relevant mechanisms, we conducted an experiment using a TgMEK6 model with MEK6 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). MEK6 overexpression in the TgMEK6 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 TgMEK6 group following MEK6 expression and the HFD, indicating the role of MEK6 expression in adipokine regulation. Plasma and bone-marrow-derived macrophages (BMDM) of the TgMEK6 group increased MEK6 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 MEK6 with HFD in fat accumulation by significantly inhibiting the mechanisms of lipolysis in the adipose and M2 associated cytokines secretion in the BMDM.
Highlights
Obesity is a state of abnormal fat accumulation resulting from converting excess energy in the body to fat
Studies have reported obesity as a factor increasing the risk of severe pneumonia and death in COVID-19 patients [9,10]
The results of MEK6 mRNA expression showed that the expression was approximately 30-fold higher in the TgMEK6/lean compared to Non-Tg/lean, and the expression was high in TgMEK6/DIO for the liver and eWATs compared to the NonTg/DIO (Figure 1B)
Summary
Obesity is a state of abnormal fat accumulation resulting from converting excess energy in the body to fat. It is caused by an energy imbalance caused by changes in various complex factors from hormones to dietary or lifestyle habits [1,2,3]. The pharmacological interventions for obesity treatment mainly focus on inhibiting the absorption and formation of lipids and controlling appetite [11], which has potential safety problems and side effects [12]. In this context, more active R&D should proceed with a focus on restoring energy balance [13]. A radical direction should be suggested for personalized obesity treatment based on identifying different markers in each individual on cellular and molecular levels with relevant gene expression
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