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Abstract
Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type 2 diabetes mellitus are global health problems. Overexpression of sterol regulatory element-binding factor (Srebf2) in transgenic animals is linked to elevated cholesterol levels and diabetes development. We investigated the impact of increased Srebf2 locus expression and the effects of control and high-fat, high-sucrose (HFHS) diets on body weight, glucose and lipid metabolisms in transgenic mice (S-mice). Wild type (WT) and S-mice were fed with both diets for 16 weeks. Plasma glucose, insulin and lipids were assessed (n = 25). Immunostainings were performed in liver, pancreas and fat (N = 10). Expression of Ldlr and Hmgcr in liver was performed by RT-PCR (N = 8). Control diet: S-mice showed reduced weight, insulin, total and HDL cholesterol and triglycerides (TG). HFHS diet widened differences in weight, total and HDL cholesterol, insulin and HOMA index but increased TG in S-mice. In S-mice, adipocyte size was lower while HFHS diet produced lower increase, pancreatic β-cell mass was lower with both diets and Srebf2, Ldlr and Hmgcr mRNA levels were higher while HFHS diet produced a rise in Srebf2 and Hmgcr levels. Srebf2 complete gene overexpression seems to have beneficial effects on metabolic parameters and to protect against HFHS diet effects.
Highlights
Mainly lipid metabolism disorders (LMD) and type 2 diabetes mellitus (T2DM), constitute a major global health problem according to the World Health Organization (WHO)
SREBP-2 mice (S-mice) under control diet showed enhanced Hmgcr levels compared with those for Wild type (WT) mice fed a control diet (Figure 6, low panel, p = 0.05). These results indicate that Srebf2 overexpression increases the mRNA levels of Srebf2, Ldlr and Hmgcr in livers of S-mice fed with a HFHS and control diet and that Srebf2 overexpression most likely increase the mRNA levels of other genes regulated by the sterol regulatory element-binding protein (SREBP)-2 system
The following differences between S-mice and other Srebf2 transgenic mice were found: moderate overexpression of Srebf2 gene regulated by its own promoter, expression in normal tissues and under own gene regulation, production of complete SREBP-2 protein and the presence of miR-33a in the genetic sequence used
Summary
There has been a fast increment in their incidence due to unhealthy lifestyle habits (sedentariness, excessive caloric intake), population ageing and genetic and epigenetic factors [1]. Nutrients 2020, 12, 3130 patients with these diseases is shorter compared to the general population [2]. The intake of a high-fat diet can lead to diet-induced obesity and metabolic disorders in humans that can be induced in the same way in rodents. In order to understand the effects of macronutrients in humans, it is important to consider their effects in mice (including the analysis in lean as well as obese ones) to clarify the pathogenesis of the metabolic disorders [3,4,5]. The sterol regulatory element-binding protein (SREBP) system is one of the main regulators of body and cellular metabolism [6]
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