Pathogenetic aspects of the development of cholelithiasis in patients with metabolic syndrome

Nowadays there is a steady tendency to increase the number of patients with gallstone disease and metabolic syndrome. Increasingly, gallstone disease is called a non-canonical cluster of metabolic syndrome, because the main components of metabolic syndrome are also modifiable risk factors for gallstone disease. This article discusses the pathogenetic parallels in the development of gallstone disease and metabolic syndrome - insulin resistance and hormones of adipose tissue, lipid metabolism disorders, immune factors and the cytokine system. There are described possible effects of cholecystectomy on metabolism in patients with metabolic syndrome.

Whey peptides exacerbate body weight gain and perturb systemic glucose and tissue lipid metabolism in male high-fat fed mice

Consumption of milk-derived whey proteins has been demonstrated to have insulin-sensitizing effects in mice and humans, in part through the generation of bioactive whey peptides. While whey peptides can prevent...

Application of Lipidomics for Assessing Tissue Lipid Profiles of Patients With Squamous Cell Carcinoma

Background: Lipid metabolism disorders play a key role in the pathogenesis of squamous cell carcinoma (SqCC). Herein we used lipidomics to study the tissue lipid profiles of 40 patients with SqCC. Methods: Lipidomics, based on ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry, was applied to identify altered lipid metabolites between tumor and adjacent noninvolved tissues (ANIT), and partial least squares-discriminant analysis model facilitated the identification of differentially abundant lipids. The area under the receiver operator characteristic curve and variable importance in projection scores of the aforementioned model were calculated to select lipid profiles. Metabolic pathway analyses were completed using Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst. Results: Differences in lipid profiles were found between tumor and ANIT, early- and advanced-stage SqCC, and positive and negative lymph node metastases. The lipid profile panel was composed of five lipids—PC(44:4), diacylglycerol(36:5), sphingomyelin(d18:1/20:0), phosphatidylinositol(46:7), and HexCer-AP(t8:0/32:2 + O)—and could effectively differentiate between tumor and ANIT. Further, pathway analyses revealed alterations in several lipid metabolism pathways, including glycerophospholipid metabolism, glycosylphosphatidylinositol anchor biosynthesis, linoleic acid metabolism, glycerolipid metabolism, and sphingolipid metabolism. Conclusion: Our data revealed several changes in the tissue lipid profiles of patients with SqCC; moreover, we identified a lipid profile panel that could effectually distinguish tumor tissues from ANIT. We believe that our results provide new insights into the biological behavior of lung SqCC.

Benefits of Anthocyanin-Rich Black Rice Fraction and Wood Sterols to Control Plasma and Tissue Lipid Concentrations in Wistar Kyoto Rats Fed an Atherogenic Diet

Background: This study reports on the relative effects of administrating a cyanidin-3-O-glucoside-rich black rice fraction (BRF), a standardized wood sterol mixture (WS), and a combination of both to lower plasma and target tissue lipid concentrations in Wistar Kyoto (WKY) rats fed atherogenic diets. Methods: Male WKY (n = 40) rats were randomly divided into five groups, which included a nonatherogenic control diet and atherogenic diets that included a positive control and atherogenic diets supplemented with BRF or WS, respectively, and a combination of both BRF + WS. Plasma and target tissue liver, heart and aorta cholesterol, and triacylglycerides (TAG) content were also measured. Results: Rats fed atherogenic diets exhibited elevated hyperlipidemia compared to counterparts fed nonatherogenic diets (p < 0.001); this effect was mitigated by supplementing the atherogenic diets with BRF and WS, respectively (p < 0.05). Combining BRF with WS to enrich the supplement lowered cholesterol similar to the WS effect (p < 0.05) and lowered TAG characteristic to the BRF effect (p < 0.05). Conclusions: Rats fed diets containing BRF or WS effectively mitigate the hypercholesterolemia and elevated TAG induced by feeding an atherogenic diet. The benefit of adding BRF + WS together is relevant to the lipid parameter measured and is target tissue-specific.

Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.

Lipids of lung and lung fat emboli of the toothed whales (Odontoceti)

Lipids are biomolecules present in all living organisms that, apart from their physiological functions, can be involved in different pathologies. One of these pathologies is fat embolism, which has been described histologically in the lung of cetaceans in association with ship strikes and with gas and fat embolic syndrome. To assess pathological lung lipid composition, previous knowledge of healthy lung tissue lipid composition is essential; however, these studies are extremely scarce in cetaceans. In the present study we aimed first, to characterize the lipids ordinarily present in the lung tissue of seven cetacean species; and second, to better understand the etiopathogenesis of fat embolism by comparing the lipid composition of lungs positive for fat emboli, and those negative for emboli in Physeter macrocephalus and Ziphius cavirostris (two species in which fat emboli have been described). Results showed that lipid content and lipid classes did not differ among species or diving profiles. In contrast, fatty acid composition was significantly different between species, with C16:0 and C18:1ω9 explaining most of the differences. This baseline knowledge of healthy lung tissue lipid composition will be extremely useful in future studies assessing lung pathologies involving lipids. Concerning fat embolism, non-significant differences could be established between lipid content, lipid classes, and fatty acid composition. However, an unidentified peak was only found in the chromatogram for the two struck whales and merits further investigation.

Novel Insights and Mechanisms of Lipotoxicity-Driven Insulin Resistance

A large number of studies reported an association between elevated circulating and tissue lipid content and metabolic disorders in obesity, type 2 diabetes (T2D) and aging. This state of uncontrolled tissue lipid accumulation has been called lipotoxicity. It was later shown that excess lipid flux is mainly neutralized within lipid droplets as triglycerides, while several bioactive lipid species such as diacylglycerols (DAGs), ceramides and their derivatives have been mechanistically linked to the pathogenesis of insulin resistance (IR) by antagonizing insulin signaling and action in metabolic organs such as the liver and skeletal muscle. Skeletal muscle and the liver are the main sites of glucose disposal in the body and IR in these tissues plays a pivotal role in the development of T2D. In this review, we critically examine recent literature supporting a causal role of DAGs and ceramides in the development of IR. A particular emphasis is placed on transgenic mouse models with modulation of total DAG and ceramide pools, as well as on modulation of specific subspecies, in relation to insulin sensitivity. Collectively, although a wide number of studies converge towards the conclusion that both DAGs and ceramides cause IR in metabolic organs, there are still some uncertainties on their mechanisms of action. Recent studies reveal that subcellular localization and acyl chain composition are determinants in the biological activity of these lipotoxic lipids and should be further examined.