In morbid obesity, reduced unstimulated and stimulated salivary flow can be observed. Bariatric surgery restored only unstimulated salivary flow to normal values. Disturbances in oxidant/antioxidant homeostasis may be observed in UWS and SWS of obese patients before and after treatment.
Objective Accelerated transmembrane transport of long‐chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid‐binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx−) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome. Methods Lipid content and fatty acid composition in each lipid subclass were estimated by gas liquid chromatography. For total, plasma membrane, and mitochondrial expression of fatty acid transporters, subfractionation with subsequent Western blot technique was used. Results A greater content of triacylglycerol in VAT of participants with obesity (MetSx−) was found. However, only the MetSx+ subjects had increased content of CER in VAT in relation to subcutaneous adipose tissue in MetSx+ and lean individuals. This was accompanied by increased total and membrane expression of FAT/CD36 in VAT in MetSx+ subjects. Accordingly, mitochondrial expression of FAT/CD36 and plasma membrane fatty acid‐binding protein was decreased in both groups of subjects with obesity. Conclusions Metabolic syndrome is associated with the accumulation of CER in VAT, possibly related to increased FAT/CD36 protein expression.
We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U-13C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment. Liver ceramide (Cer), diacylglycerol (DAG) and acyl-carnitine concentration and enrichment were analyzed by LC/MS/MS. The content of proteins involved in lipid metabolism and insulin signaling were analyzed by Western Blot. HFD treatment increased the content and FSR of DAG and Cer in the liver which was accompanied by systemic insulin resistance and inhibition of hepatic insulin signaling pathway under insulin stimulation. Metformin treatment ameliorated systemic insulin resistance and augmented the hepatic insulin signaling cascade. It reduced both the concentration and FSR of Cer, DAG, and increased acyl-carnitine content and the expression of mitochondrial markers. We postulate, that in liver, the insulin sensitizing effect of metformin depends on augmentation of mitochondrial β-oxidation, which protects from hepatic accumulation of both the Cer and DAG and preserves insulin sensitivity under HFD consumption. Moreover, we showed that hepatic content of Cer and DAG corresponds with their respective FSR.
Ceramide accumulation in muscle and in liver is implicated in the induction of insulin resistance. Much less in known about the role of ceramide in adipose tissue. The aim of the present study was to elucidate the role of ceramide in adipose tissue and to clarify whether lipids participate in the regulation of adipocytokine secretion. The experiments were performed on male Wistar rats divided into three groups: 1. Control, 2. fed high fat diet (HFD), and 3. fed HFD and treated with myriocin. Ceramide (Cer) and diacylglycerol (DAG) content were analyzed by LC/MS/MS. Hormone sensitive lipase (HSL) phosphorylation was analyzed by Western Blot. Plasma adiponectin and tumor necrosis factor alpha (TNF-α) concentration were measured by enzyme-linked immunosorbent assay. An oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) was also performed. In HFD group, total DAG and Cer content was elevated in both subcutaneous and visceral adipose tissue, which was accompanied by increased glucose, insulin, and HOMA-IR value. Myriocin treatment restored HOMA-IR as well as glucose and insulin concentration to control values. Moreover, myriocin decreased not only Cer, but also DAG levels in both fat depots. Furthermore, we observed a strong correlation between adiponectin (negative) and TNF-α (positive) and Cer in both fat tissues, which suggests that Cer is involved in the regulation of adipocytokine secretion.
Liver, as one of the most important organs involved in lipids and glucose metabolism, is perceived as a key tissue for pharmacotherapy of insulin resistance (IRes) and type 2 diabetes. Ceramides (Cer) are biologically active lipids, which accumulation is associated with the induction of muscle IRes. We sought to determine the role of intrahepatic bioactive lipids production on insulin action in liver of insulin-resistant rats and after myriocin administration. The experiments were conducted on male Wistar rats divided into three groups: Control, fed high-fat diet (HFD), and fed HFD and treated with myriocin (HFD/Myr). Before sacrifice, the animals were infused with a [U- C]palmitate to calculate lipid synthesis rate by means of tracer incorporation technique in particular lipid groups. Liver Cer, diacylglycerols (DAG), acyl-carnitine concentration, and isotopic enrichment were analyzed by LC/MS/MS. Proteins involved in lipid metabolism and insulin pathway were analyzed by western blot analysis. An OGTT and ITT was also performed. HFD-induced IRes and increased both the synthesis rate and the content of DAG and Cer, which was accompanied by inhibition of an insulin pathway. Interestingly, myriocin treatment reduced synthesis rate not only of Cer but also DAG and improved insulin sensitivity. We conclude that the insulin-sensitizing action of myriocin in the liver is a result of the lack of inhibitory effect of lipids on the insulin pathway, due to the reduction of their synthesis rate. This is the first study showing how the synthesis rate of individual lipid groups in liver changes after myriocin administration.
chronic conditions including diabetes, cardiovascular diseases, depression, and cancers. 1 In addition, people with obesity are at a higher risk of gastroesophageal reflux disease (GERD) and its complications such as Barrett esophagus and esophageal adenocarcinoma. Body mass index (BMI), waist-to-hip ratio, or visceral adiposity are linked to GERD symptoms, Barrett esophagus, or esophageal adenocarcinoma. 3-6 INTRODUCTION The increasing prevalence of obesity in adults in developing countries, and in children and adolescents globally, is a major public health challenge. 1,2 In Poland, every fourth inhabitant is obese and abdominal obesity is observed in every third man and nearly every second women. 2 The estimated health care costs attributable to excessive body weight are high because obesity is associated with increased risks of major
Popularity of laparoscopic sleeve gastrectomy (LSG) has been growing gradually. The aim of this study was to determine changes in metabolic syndrome parameters as well as insulin, total cholesterol, and LDL cholesterol, and to describe the influence of body weight loss on co-morbidities in obese patients after LSG with 1-year follow-up. The material consists of 130 patients who underwent LSG (2007–2010) in order to treat morbid obesity and who had met before the surgery at least three criteria necessary for the diagnosis of metabolic syndrome according to the International Diabetes Federation. The influence of LSG on co-morbidities was also analyzed. During 1-year follow-up after LSG, we obtained a statistically significant decrease in BMI (from 53.18 ± 7.5 kg/m2 to 31.4 ± 3.75 kg/m2, p < 0.00001) and a reduction in waist circumference. Twelve months after the surgery, excess weight loss (EWL) was 59.42 ± 7.21% and excess body mass index loss (EBL) was 61.03 ± 6.50%. One year after LSG, the amount of patients with diagnosed metabolic syndrome decreased in 61 patients (53.08%). After 1 year, none of the patients met five criteria of metabolic syndrome. According to efficiency in body mass loss presented by %EWL and %EBL, LSG is gaining approval as a method of obesity and metabolic syndrome treatment, although it is a relatively new procedure. LSG is rather an easy procedure; the time of performance and hospitalization are shorter which entails normalization in all parameters of metabolic syndrome and decreases the percentage of obese patients with metabolic syndrome.
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