Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue

Abstract

The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people’s health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger–ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.

From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation

“…For instance, 1,25(OH) 2 D 3 can upregulate the expression of TLR2 and TLR4 on human monocytes [ 98 , 99 ]. In an animal study, the intervention, i.e., vitamin D and regular exercise, decreased the expression of FATP4 (fatty acid transport protein 4) and TLR4 in both AT and the liver [ 100 ]. In obesity, regulating TLR levels in AT may have an impact on the susceptibility of cells to inflammatory stimuli.…”

Inhibition of Hyperglycemia and Hyperlipidemia by Blocking Toll-like Receptor 4: Comparison of Wild-Type and Toll-like Receptor 4 Gene Knockout Mice on Obesity and Diabetes Modeling

“…Previous studies demonstrate that TLR4 is distributed in various tissues and organs, including the liver, intestine, and adipose tissue, and an increase in the expression of TLR4 was observed in the liver and adipose tissues of obese rats and mice fed with a high-fat diet [21,38,39]. The overexpression of TLR4 is associated with the accumulation of fat granules in the liver and lipid degeneration of liver cells, which has been verified in non-alcoholic steatohepatitis of mice or rats [21,39,40]. Gut microbiota Prevotella copri colonization could increase fat accumulation in pigs by activating TLR4 signaling pathways to increase the permeability of the intestinal barrier and cause a chronic inflammatory response in the host.…”

“…The accumulation of lipids in the body is closely related to the development of obesity, which is determined by the capability of lipid metabolism [37]. Previous studies demonstrate that TLR4 is distributed in various tissues and organs, including the liver, intestine, and adipose tissue, and an increase in the expression of TLR4 was observed in the liver and adipose tissues of obese rats and mice fed with a high-fat diet [21,38,39]. The overexpression of TLR4 is associated with the accumulation of fat granules in the liver and lipid degeneration of liver cells, which has been verified in non-alcoholic steatohepatitis of mice or rats [21,39,40].…”

“…Inhibiting the expression of related inflammatory factors by blocking the TLR4 signaling pathway may have a preventive effect on metabolic diseases [17][18][19]. Obesity-induced inflammation is mainly activated by the TLR4 signaling pathway, which in turn activates the downstream pathway nuclear factor kappa B (NF-κB) and causes the production of pro-inflammatory factor TNF-α, further aggravating the inflammation [20,21]. Studies have demonstrated that TLR4 deficiency can alleviate inflammation and insulin resistance in adipose tissue, and inhibit liver steatosis [22].…”

Exploring the NRF2/HO-1 and NF-κB Pathways: Spirulina Nanoparticles as a Novel Approach to Combat Diabetic Nephropathy

“…Thirty-six male Wistar rats (175–185g, 55 ± 2 days) were housed in plastic cages with plenty of ventilation, provided unrestricted access to food and water, and subjected to a 12/12 h cycle of darkness and light each day at 27 ± 2 °C in this experiment. The standard rat chow diet provided by Al-Gomhoureya, Cairo, Egypt, consists of 306.2 kcal per 100 g, with 48.8% carbohydrates, 21% protein, and 3% fat . The rats were adapted for 2 weeks.…”