br Results Table shows demographics and clinical features of

Results Table 1 shows demographics and clinical features of subjects with obesity and controls. Before surgery five obese were diabetic, only one on glucose-lowering therapy; three obese were dyslipidemic and assumed lipid lowering medications. Lathosterol levels were significantly higher in patients with obesity while sitosterol levels were significantly lower; campesterol levels did not differ significantly in the two groups. As shown in Table 2 after surgery we observed significant drops in BMI, waist circumference, visceral and subcutaneous fat, systolic and diastolic blood pressure, triglycerides, glycemia, serum insulin and HOMA index. Apoprotein AI and HDL-C levels increased significantly. Lathosterol levels decreased significantly, while cholesterol filgotinib markers were not significantly modified. After surgery we observed diabetes remission in all diabetic subjects; only one dyslipidemic subject continued to assume lipid lowering medications. Lipid and calorie intake patterns before and after sleeve gastrectomy are shown in Fig. 1. In univariate correlation analysis lathosterol showed a significant positive correlation with BMI, visceral fat area and HOMA-IR (Fig. 2).
Discussion The present study confirms that severe obesity is closely associated with the metabolic features of insulin-resistance and that insulin-resistance is associated with high cholesterol synthesis and low cholesterol absorption [10]. The present study is the first to assess cholesterol synthesis and absorption modifications after LSG. The main finding was that, besides reducing BMI and improving insulin-resistance, LSG reduced cholesterol synthesis. Although often included among restrictive procedures LSG is not comparable to gastric banding because it removes about 80% of the stomach. The LSG-induced drop in cholesterol synthesis could be due to insulin-resistance correction, as has been observed after mixed-type bariatric surgery procedures. The decrease in cholesterol synthesis was not associated with a compensatory rise in cholesterol absorption, probably because removal of most of the stomach, causes cholecystokinin production to drop and thus reduce cholesterol absorption [3]. In our view LSG should not be considered merely a restrictive procedure, as its beneficial effects are similar to those of the Roux-en-Y gastric bypass, even though it impacts less on malabsorption.
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Acknowledgement
The liver and the intestine have important roles in regulating cholesterol levels. The liver is a major site for sterol biosynthesis and production, uptake of lipoproteins, and metabolism of cholesterol to bile acids (BAs)., , , The intestine also maintains whole-body cholesterol levels by mediating intestinal absorption of dietary and biliary cholesterol and also by direct transintestinal cholesterol excretion (TICE)., , , , These processes are regulated by interactions between the liver and intestine. In response to a meal, the BA-activated nuclear receptor farnesoid X receptor (FXR, NR1H4) induces expression of intestinal fibroblast growth factor (FGF) 19 (human FGF19, mouse FGF15), which acts at the liver and regulates the expression of target genes important for cholesterol and BA metabolism, including NR0B2 (nuclear receptor subfamily 0 group B member 2), also known as SHP (small heterodimer partner)., , , SHP is an unusual nuclear receptor that does not have a DNA binding domain but acts as a corepressor for numerous transcriptional factors, including LRH-1 (liver receptor homolog-1), SREBF2 (sterol regulatory element binding transcription factor, also known as SREBP-2), and aryl hydrocarbon receptor., , SHP mediates epigenomic repression of genes by recruiting repressive histone-modifying proteins., , As an orphan nuclear receptor, endogenous ligands of SHP are unknown, but its nuclear localization and gene-repressive function are enhanced by posttranslational modifications in response to postprandial FGF15/19 signaling., , , SHP is well known to repress hepatic BA production,, , , but it is also involved in hepatic lipid metabolism, inflammation, and circadian regulation of metabolism., , , Recent genomic and follow-up studies of mice treated with FGF19 showed new hepatic functions of SHP and FGF19 in the inhibition of sterol biosynthesis, 1-carbon metabolism, and autophagy., , SHP and FGF19 repress both cholesterol conversion into BA and sterol biosynthesis in the liver,, , but intestinal functions of the FGF19-SHP axis in cholesterol regulation have not been reported.